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Lymphoproliferative disease virus (LPDV) was first documented in wild turkeys in North America in 2009. LPDV infection is often subclinical but can manifest as lymphoid proliferation or round cell neoplasia. Despite high prevalence across many sampled areas corresponding to declining populations of wild turkeys, knowledge regarding LPDV pathogenesis, risk factors for disease development, and associated impacts on population dynamics are unknown. To understand transmission, viral shedding, and tissue tropism, we inoculated 21 domestic turkeys via the oral cavity, crop, nasal cavity, subcutis, or coelomic cavity. For 12 weeks, oropharyngeal swabs, cloacal swabs, and whole blood were collected weekly. At 1 week postinoculation, 3 turkeys (3/21; 14%) had detectable LPDV proviral DNA in blood by polymerase chain reaction, and 10 developed DNAemia (50%; 10/20) by 12 weeks. LPDV proviral DNA was intermittently detected in oropharyngeal and cloacal swabs. Splenomegaly was the most consistent gross finding in DNAemic birds (8/11; 73%). Lymphoid hyperplasia in the spleen was the most significant microscopic finding (9/11; 82%). Three turkeys (3/11; 27%) developed round cell neoplasia characterized by sheets of pleomorphic, round to polygonal cells in the adrenal gland, bone marrow, skin, small intestine, and/or spleen. LPDV was detected in the spleen and bone marrow from all turkeys with DNAemia and all neoplasms. Our study establishes that infection and disease with North American LPDV from wild turkeys can be experimentally reproduced in domestic turkeys, laying the groundwork for future investigations into LPDV pathogenesis, development of diagnostic techniques, and understanding the impacts of LPDV on wild turkey populations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients., Methods: We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups., Results: Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival., Conclusion: Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages., Methods: In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing., Results: In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D., Conclusion: Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Darwish et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

Although it is known that BK polyomavirus (BKPyV) causes hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of BKPyV viremia has not been fully evaluated. We retrospectively analyzed the results of quantitative polymerase chain reaction (PCR) evaluations for detecting BKPyV in the whole blood samples of patients undergoing allogeneic HSCT during the period from January 2010 to June 2020 at a single institute, Tokyo Medical and Dental University. BKPyV was detected in the blood of 28 of the 107 evaluated patients, and the cumulative incidence of was 27.9% (95%CI: 20.2-37.9%). HC due to BKPyV developed in four of the 28 patients with BKPyV viremia (14.3%) and in two of the 79 patients without it (2.5%; P < 0.05). BKPyV viremia itself did not affect the patients' post-transplant estimated glomerular filtration rate (eGFR), but BKPyV viremia with a high viral load was significantly associated with decreased eGFR values (P < 0.05). BKPyV viremia was also associated with significantly lower progression-free survival at 3 years (35.1% [95%CI: 17.8-53.1%] vs. 60.4% [95%CI: 48.4-70.5], P < 0.05). Our findings demonstrated that BKPyV viremia was associated with onset of HC, an early decline of renal function, and poorer survival after allogeneic HSCT. Further studies are needed to test these results and elucidate the mechanisms of renal dysfunction associated with BKPyV viremia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Avian polyomavirus (APV) infection causes various health problems in psittacine species, including death. The present study was conducted to investigate the prevalence of APV among psittacine birds in Iran. We also aimed to evaluate the impact of age, sex, species, season, and origin of the birds on the prevalence of APV. This study investigated the presence of APV among 1050 individual birds from 7 psittacine species over a 1-year period in Iran, namely, green-cheeked parakeets ( Pyrrhura molinae ), rosy-faced lovebirds ( Agapornis roseicollis ), monk parakeets ( Myiopsitta monachus ), sun conures ( Aratinga solstitialis ), Senegal parrots ( Poicephalus senegalus ), cockatiels ( Nymphicus hollandicus ), and grey parrots ( Psittacus erithacus ). The overall prevalence of APV in all studied species was 25% (263/1050, 95% confidence interval [CI]: 22.5-27.8). Results of the study showed that age and the season of the year were 2 important determinant factors in the prevalence of APV in psittacine birds. Young psittacine birds <6 months old were 2.94 (95% CI: 1.19-7.27) times more likely to be infected with APV than birds >1 year old, and there was a significant interaction between season and species in the multivariate analysis. In the winter season, rosy-faced lovebirds and green-cheeked parakeets were 15.6 (95% CI: 4.20-57.95) and 4.76 (95% CI: 1.4-16.21) times more likely to be infected with APV than in other seasons, respectively. This is the first report on the detection rate of APV in psittacine birds in Iran.

Introduction: Breast cancer, a pervasive invasive carcinoma among women globally, afflicts approximately 12% of women worldwide. Previous studies have indicated that certain viruses, including oncogenic viruses such as polyomaviruses BK and JC, may play a role in the development of breast cancer. In light of this, the present study endeavors to assess the incidence of BKV and JCV virus in breast cancer patients., Materials and Methods: One hundred formalin-fixed paraffin-embedded tissue samples were procured and subjected to deparaffinize by xylene, followed by DNA extraction through the phenol-chloroform methodology. Detection and genotyping of BKV and JCV were carried out utilizing specific primers via PCR analysis., Results: Merely 2 out of 100 (2%) ductal carcinoma in situ with grade 2 specimens exhibited positivity for BK virus genotype IV, whereas JC virus DNA was not discerned across all the samples., Discussion: The findings of the current investigation demonstrate that there was an absence of JC virus detection in the breast biopsy. Additionally, a small fraction of patients diagnosed with ductal carcinoma exhibited a low prevalence of genotype IV polyomavirus BK at a rate of 2%. However, in order to gain a more comprehensive understanding of the incidence of BKV and JCV in breast cancer, a substantial number of breast samples must undergo investigation.

Background: BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients., Methods: We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m 2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized., Results: Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m 2 ., Conclusions: BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective and Background: BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients., Methods: We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC., Results: Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I 2  = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I 2  = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I 2  = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I 2  = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I 2  = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I 2  = 79%) were significantly associated with BKV-HC in the univariable analysis., Conclusions: Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

As a therapeutic method, kidney transplantation significantly improved the life quality and prognosis of patients with the end-stage renal disease. Since a key element in stable kidney transplantation is continuous therapy with immunosuppressive agents, an inhibited immune response makes patients vulnerable to opportunistic viral and bacterial infections. Polyomavirus (PyV), from the Polyomaviridae family, includes a well-known BK virus (BKPyV) and less publicized human polyomavirus 9 (HPyV9). Both these viruses may inflict significant damage to kidney transplants because of their high prevalence and pathogenesis. While a great body of knowledge was accumulated about the BKPyV-caused nephropathy, much less information is about the potential threat from the HPyV9-caused damage to kidney transplants. The current review provides a glimpse of general information about the PyV-associated nephropathy with a special focus on the role of the HPyV9 in pathogenesis of nephropathy in kidney transplants., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study aimed to explore the risk factors for BK virus (BKV) infection in renal transplant recipients (RTRs) routinely treated with tacrolimus., Methods: Forty-two cases with BKV infections and 51 patients without BKV infections were enrolled in the study. Eighty-seven healthy individuals and 77 patients undergoing dialysis were randomly included as controls. A logistic regression model was used to analyze potential variables in order to evaluate factors related to BKV infection in the renal transplant recipients., Results: The number of individuals with acute rejection in BKV positive RTRs is significantly higher than that in BKV negative RTRs. Hemoglobin levels in BKV positive RTRs were significantly lower than those in BKV negative RTRs (109.61 ± 20.11 vs. 130.16 ± 26.297, p < 0.001). There was a positive correlation between tacrolimus levels and hemoglobin concentration in RTRs (r = 0.329, p = 0.023). The results of a multivariate regression analysis indicated that a history of acute rejection (OR = 4.157, p = 0.031) and low hemoglobin (OR = 0.963, p < 0.001) were risk factors for BKV infection., Conclusions: Acute rejection and low hemoglobin were risk factors for BKV infection after renal transplantation.

Objective: To analyze high-risk factors affecting BK polyomavirus (BKPyV) infection and to construct a prediction model for BKPyV infection in children after renal transplantation. Methods: The clinical data of 332 children who received allogeneic kidney transplantation in the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2022 were retrospectively collected. According to the BKPyV load level, the dynamic change process of lymphocytes at different time points were analyzed. The factors that have potential influence on BKPyV infection were screened by Cox regression analysis, and the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of the predictive model of infection. Results: Among the 332 children, there were 215 males and 117 females; the age of transplantation was (12.2±3.9) years old; 37 cases were preschool (1-5 years old), and 295 cases were post-school age (6-18 years old). BKPyV load in 224 urine samples and 30 blood samples of children were detected. There were 9 cases of BKPyV-associated viruria and 3 cases of BKPyV associated viremia in pre-school children, 76 cases BKPyV associated viruria and 14 cases of BKPyV associated viremia in post-school children. Multivariate Cox regression analysis showed that higher body mass index (BMI) ( HR =1.105, 95% CI : 1.020-1.197), antithyroglobulin (ATG) application ( HR =2.196, 95% CI : 1.335-3.613), and higher tacrolimus concentration ( HR =2.484, 95% CI : 1.298-4.753), higher natural killer (NK) lymphocyte count ( HR =1.193, 95% CI : 1.009-1.411), higher CD14 ++ CD16 - cell count ( HR =1.096, 95% CI : 1.024-1.173) were independent risk factors for BKPyV associated viruria in post-school children. Delayed graft function (DGF) ( HR =4.993, 95% CI : 1.555-16.038), Acute rejection (AR) ( HR =6.021, 95% CI : 1.930-18.787), higher CD14 ++ CD16 - cell count ( HR =1.227, 95% CI : 1.081-1.392) were independent risk factors for BKPyV associated viremia in post-school children. The results of ROC curve analysis showed that combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, and CD14 ++ CD16 - cell count predicted the occurrence of BKPyV associated viruria in post-school children after kidney transplantation at 0.5, 1, 2, and 5 years with area under curve (AUC) of 0.712 (95% CI : 0.626-0.798), 0.708 (95% CI : 0.612-0.804), 0.754 (95% CI : 0.668-0.840) and 0.767 (95% CI : 0.685-0.849). The sensitivity and specificity of the model were 64.9%, 61.4%, 61.6%, 55.8% and 70.9%, 72.4%, 76.0%, 84.0%, respectively. Combined with DGF, AR, and CD14 ++ CD16 - cell counts predicted the occurrence of BKPyV-associated viremia at 0.5, 1, 2, and 5 years after renal transplantation in post-school children with AUC of 0.791 (95% CI : 0.631-0.951), 0.744 (95% CI : 0.547-0.936), 0.786 (95% CI : 0.629-0.946) and 0.812 (95% CI : 0.672-0.948). The sensitivity and specificity of the model were 76.1%, 67.1%, 75.0%, 77.9% and 88.9%, 89.0%, 89.9%, 88.0%, respectively. Conclusions: The postoperative CD14 ++ CD16 - cell level can be used as an independent predictor of BKPyV infection in post-school children after renal transplantation. Combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, CD14 ++ CD16 - cell count and combined DGF, AR, CD14 ++ CD16 - cell count show good fitting effect in predicting the occurrence of BKPyV-associated viruria and viremia after transplantation in post-school children respectively.

BACKGROUND BK infections have been observed more frequently among people who are rapid metabolizers. The tacrolimus c/d ratio identifies rapid metabolizers after transplantation. Envarsus has a lower peak drug level exposure than tacrolimus and is more pronounced in rapid metabolizers. This study hypothesized that less exposure to high tacrolimus levels through use of Envarsus would reduce the incidence of BK infections. MATERIAL AND METHODS This study prospectively converted 43 consecutive kidney transplant recipients (identified as rapid metabolizers by c/d ratio of.

Background: Polyomavirus, known as BK virus, is an important cause of allograft dysfunction in renal transplant patients, leading to BK virus nephropathy. The main study objectives were to assess the disease incidence and disease course in pediatric patients, and assess the diagnostic accuracy of BK screening for asymptomatic patients., Methods: This is a single-center observational study, which included 81 pediatric renal allograft recipients that were transplanted and/or followed at King Fahad Specialist Hospital-Dammam, Saudi Arabia. Screening for BK virus was performed prospectively according to a predetermined hospital protocol. Our BK screening protocol consisted of periodic quantitative real time polymerase chain reaction test in the plasma. In patients with deranged graft function, graft biopsies were evaluated for the presence of BK nephropathy., Results: Our study detected BK viremia in 14 patients (17.3%), while BK nephropathy occurred in seven patients (8.6%). The onset of BK viremia had bimodal distribution, 78 percent occurring within first year post-transplantation, while 21.4% occurred late. Patients who developed BK nephropathy had a higher BK level than BK viremia patients, for both mean and peak values (p = .02, p = .02). A BK cutoff level of 40 000 copies/mL showed sensitivity and specificity of 85.7%, 85.7%, respectively, in predicting the conversion of BK viremia to BK nephropathy., Conclusions: BK viremia and BK nephropathy occur in pediatric patients with similar incidence rates compared to adult patients. Protocolized screening led to early detection of viremia, and could predict the conversion of BK viremia to BK nephropathy and allow for early immunosuppression modulation., (© 2023 Wiley Periodicals LLC.)

Background: Following kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR., Methods: We conducted a retrospective case-control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan-Meier estimator., Results: Sixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5-14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm 3 and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01)., Conclusions: BKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm 3 and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis., (© 2023. The Author(s).)

Background: BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use., Methods: Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use., Results: Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased., Conclusion: BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose., (© 2022 Wiley Periodicals LLC.)

Background: Leukemia patients are immune-compromised even before starting chemotherapy because the malignant cells invade the bone marrow and destroy WBC precursors. Leukemic patients are more susceptible to infection by a wide range of microorganisms. Viral infections and reactivations are common and may result in severe complications. The aim of this study is to investigate different causes of viremia in ALL pediatric patients as well as the clinical and the laboratory characteristics associated with viral infections., Methods: Qualitative real-time PCR was used to detect (polyoma BK, parvo B19 and herpes simplex virus) DNA in the blood of ALL patients and routine hospital records were used to provide the data of hepatitis B & C virus infection., Results: Polyoma BK was the most common detected virus (51.2%) followed by herpes simplex (30.2%). Viremia by single virus was found in 16 (37.2%) cases, while viremia by multiple viruses was found in 15 (34.8%) cases. The most frequent co-detected viruses were herpes simplex and polyoma BK (11.6%) followed by herpes simplex, parvo B19 and polyoma BK (9.3%)., Conclusion: There is a high frequency of viremia by single virus and viremia by multiple viruses at the time of diagnosis of acute lymphoblastic leukemia in pediatric patients admitted to South Egypt Cancer Institute (SECI) compared to studies in other regions. Polyoma BK is the most common detected virus and is mainly associated with lymphopenia. It was also significantly associated with herpes simplex viremia. HCV infection was associated with increased incidence of CNS leukemia., (© 2022. The Author(s).)

Colorectal cancer is ranked to have high mortality among most malignancies worldwide. In the adult population, the seroprevalence rates of the John Cunningham virus (JCV) range from 70% to 90%. Recently the association for JCV in many malignant tumours have been reported worldwide, including colonic and rectum cancers. Interleukin-1β (IL-1β) can promote tumour growth where it is abundant in the tumour microenvironment, and its up-regulation is considered a poor prognostic feature in different types of solid tumours, including colon malignancies. One hundred tissue biopsies belonged to 50 patients with colorectal cancers and 30 benign colonic tumour patients, and 20 colorectal control tissues were enrolled in this study. JCV was detected via chromogenic in situ hybridization (CISH), while IL-1 beta was detected by immunohistochemistry (IHC). The recorded data showed that 21 out of 50 (42%) tissue samples with colorectal carcinoma showed positive CISH reactions for JCV DNA in this study. The benign colorectal tumours group revealed positive signals in 2 out of 30 tissues representing 6.7% of this group. Lastly, no control tissues showed positive signals for the JCV -CISH test. The positive signals of IL-1 Beta-IHC detection were found in 26 out of 50 (52 %) colorectal carcinoma tissues, while in the benign colorectal tumour was 43.3% (13 out of 30) and in AHC was 20% (4 out of 20 tissues). The high rates of JCV infection in this group of Iraqi patients with colonic adenocarcinoma in concordance with IL-1 Beta expression could play an essential role in the development and progression of these malignant tumours along with benign colonic tumours. To analyze the concordant expression of IL-1 beta gene and JCV in issues from a group of Iraqi patients with colonic adenocarcinomas., Competing Interests: The authors declare that they have no conflict of interest.

BK polyomavirus (BKPyV) is a well-known cause of nephropathy in renal transplant recipients. It has recently received much attention from researchers as a major predisposing factor for various cancers. This study aimed to investigate how BKPyV affected the advancement of papillary thyroid carcinoma (PTC). A total of 1057 samples were tested for BKPyV DNA and RNA, comprising 645 paraffin-embedded PTC biopsy samples (PEBS), 412 fresh biopsy samples (FBS), and 1057 adjacent noncancerous samples. The BKPyV DNA was found in 511 (48.3%) of the specimens, including 347 (84.2%) FBS and 164 (25.4%) PEBS. The mean BKPyV copy number was significantly lower in patients with PEBS (0.5 × 10 -4  ± 0.1 × 10 -4  copies/cell) than in FBS (1.3 × 10 -1  ± 0.2 × 10 -1  copies/cell) and non-PTC normal samples (0.3 × 10 -5  ± 0.04 × 10 -5  copies/cell). The PEBS had lower LT-Ag RNA expression than FBS, and no VP1 gene transcript expression was detected. In conclusion, although our findings indicated the presence of BKPyV in some Iranian PTC patients, more research is needed to corroborate these findings., (© 2022 Wiley Periodicals LLC.)

BK viremia is endemic among kidney transplant recipients (KTRs). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era. This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥10 3 copies/ml constituted high viremia. Among 1193 KTRs, the cumulative probability of developing detectable and high BK viremia within 2 years posttransplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), nondepleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 ml/min/1.72 m 2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, antiproliferative dose reductions were the most common initial management. BK viremia remains a common early complication in a modern cohort of KTRs. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation., (© 2022 Wiley Periodicals LLC.)

Background: Cytochrome P450 3A5 (CYP3A5) includes two active genotypes, namely CYP3A5*1/*1 or *1/*3 with the fast metabolic activity and CYP3A5*3/*3 with slow metabolic. We retrospectively analyzed the correlation between CYP3A5 gene polymorphism and the susceptibility to the BK virus (BKV) infection in renal transplant recipients., Methods: According to the inclusion/ exclusion criteria, we selected 134 recipients who received kidney transplantation at the Renmin Hospital of Wuhan University from January 2019 to December 2019. Based on the pre-operative CYP3A5 sequencing results, 134 recipients were divided into two groups: those expressing the fast metabolic CYP3A5*1/*1 or *1/*3 genotype; and, those expressing slow metabolic CYP3A5*3/*3 genotype. These two recipient groups were then analyzed for the BKV infection rate with different metabolic types to establish the potential relationship between CYP3A5 gene polymorphism and BKV infection., Results: The overall incidence of BKV viruria was 37.3%, whereas BKV viremia was 4.5% among all 134 recipients. The fast metabolism group had 9.1% incidence of BKV viremia and 49.1% incidence of BKV viruria. In contrast, the slow metabolism group had only 1.3%incidence of BKV viremia (P = 0.031) with only 29.1% BKV viruria (P = 0.011). The incidence of low levels of urinary BKV in the fast metabolism group was higher than that in the slow metabolism group (P = 0.005), while no significant statistical difference in the incidence of high levels of urinary BKV and high and low levels of blood BKV., Conclusion: After kidney transplantation, CYP3A5 gene polymorphism of recipients present a certain relationship with the occurrence of BKV infection, which may be of value for the prediction and prevention of BKV infection., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Our aim was to study the seroprevalence of human polyomaviruses (HPyV) linked to skin diseases. A total of 552 serum samples were analysed by the enzyme-linked immunosorbent assay to detect IgG antibodies against Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7 and Trichodysplasia spinulosa-associated polyomavirus (TSPyV) using recombinant major capsid proteins of these viruses. The individuals (age 0.8−85 years, median 33) were sorted into seven age groups: <6, 6−10, 10−14, 14−21, 21−40, 40−60 and >60 years. The adulthood seroprevalence was 69.3%, 87.7%, 83.8% and 85% for MCPyV, HPyV6, HPyV7 and TSPyV, respectively. For all four polyomaviruses, there was increasing seropositivity with age until reaching the adulthood level. There was a significant increase in seroreactivity for those age groups in which the rate of already-infected individuals also showed significant differences. The adulthood seropositvity was relatively stable with ageing, except for TSPyV, for which elevated seropositivity was observed for the elderly (>60 years) age group. Since seroepidemiological data have been published with wide ranges for all the viruses studied, we performed a comprehensive analysis comparing the published age-specific seropositivities to our data. Although the cohorts, methods and even the antigens were variable among the studies, there were similar results for all studied polyomaviruses. For MCPyV, geographically distinct genotypes might exist, which might also result in the differences in the seroprevalence data. Additional studies with comparable study groups and methods are required to clarify whether there are geographical differences.

Background & Objectives: BK virus (BKV) is a polyomavirus and cause of a common infection after renal transplantation which could be preceded to BKV-associated nephropathy. It has four main subtypes (I-IV). BKV subtypes II and III are rare, whereas subtype I shows a ubiquitous distribution. The objective of the present study was to investigate the prevailing BKV subtypes and subgroups in renal transplant patients in Sri Lanka., Methods: The presence of BKV in urine was tested through virus load quantification by real-time PCR from 227 renal transplant patients who were suspected to have BKV infection. Of these patients only 41 were found to be BKV infected (>10 3 copies/ml) and those were subjected to conventional PCR amplification of VP1 gene followed by BKV genotyping via phylogenetic analysis based on DNA sequencing data., Results: Persistent BK viral loads varied from 1×10 3 to 3×10 8 copies/ml. Of the 41 patient samples, 25 gave positive results for PCR amplification of subtyping region of VP1 gene of BKV. BKV genotyping resulted in detecting subtype I in 18 (72%) and subtype II in seven (28%) patients. BKV subgroups of Ia, Ib-1 and Ib-11, and Ic were identified with frequencies of 6/18 (33.3%), 6/18 (33.3%), 5/18 (27.8%), and 1/18 (5.6%), respectively., Interpretation & Conclusions: Findings from this preliminary study showed a high occurrence of subtype I, while the presence of subtype II, which is rare and less prevalent, was a novel finding for this Asian region. This emphasizes the need for further molecular and serological studies to determine the prevalence of different BKV subtypes in Sri Lanka.

Background: BKV and BKVN are common in pediatric kidney transplant, but there is limited data on treatment approaches. Our objective was to study the prevalence of BKV and BKVN utilizing only plasma qPCR and report treatment outcomes with stepwise IR and IVIG., Methods: A retrospective study of all pediatric kidney transplants from 2013 to 2020. Excluded patients >21 years at transplant and immediate graft failure. Surveillance was conducted using only plasma BK qPCR at 1, 3, 6, 9, 12, 18, and 24 months and annually. BKV defined as ≥250 copies/ml and resolution as <250 copies/ml. Presumed BKVN as >10 000 copies/ml despite IR; and BKVN if confirmed on histology., Results: Fifty-six patients were included in the study; 20 (35.7%) had BKV. BKV was associated with longer duration of stent, 40 vs. 33.5 days (p = .004). Two patients (3.5%) had confirmed, and 2(3.5%) had presumed BKVN. The first-line treatment was IR in 100% of patients. BKVN confirmed and presumed received IVIG every month for six doses. Viral resolution was achieved in 70%, and no difference was noted in estimated glomerular filtration rate between BKV and non-BKV group (p = .438). There were no rejection episodes, and graft survival was 100% over median follow-up of 3 years., Conclusions: Plasma qPCR alone is adequate for screening and monitoring treatment of BKV and BKVN. A stepwise IR and IVIG resulted in BKV resolution in the majority of patients. Larger studies are required to study the role of IVIG in the treatment of BKVN., (© 2022 Wiley Periodicals LLC.)

Background: Improved short- and long-term outcomes of kidney transplantation have been achieved over the past decades due to improved immunosuppression. This may have increased the risk for infections and, particularly, for the viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma BK virus (BKV)., Methods: A retrospective review of viremic CMV, EBV, and BKV infections in pediatric renal transplant recipients treated and followed by a national referral center over a 10-year period., Results: Sixty-seven patients (68% males) received 68 kidney grafts (62% from living donors) during the study period; the mean follow-up period was 5.2 ± 2.4 years. Twenty-seven viremic episodes were documented (CMV: 13, EBV: 6, BKV: 8) in 24 patients (35.2%). The median time (interquartile range) to viremia post-transplant was 11 (4-38) months. The viral infection rate was significantly higher in the years 2014-2015 than in previous years (61% vs. 29%, p = .017). Compared to patients who did not develop viremia, patients with viremias were younger at the time of transplantation, were more likely to receive thymoglobulin induction pre-transplant and to develop an acute rejection. Multiple logistic regression modeling identified transplant year and recipient's age as significant risk factors for viremia. Graft outcome and eGFR at the last follow-up was similar between patients who did and did not develop viremia., Conclusions: Viral infections continue to be a major cause of morbidity in pediatric kidney transplant recipients. However, with close monitoring and prompt intervention, patient and renal outcomes remain favorable., (© 2021 Wiley Periodicals LLC.)

Objectives: BK polyomavirus infection is a critical complication affecting graft survival after kidney transplant. We aimed to determine the frequency, the effect on graft function, and the risk factors of BK polyomavirus infection in pediatric kidney transplant patients., Materials and Methods: We retrospectively reviewed data of 144 pediatric patients (female/male: 67/77; 0-18 years of age) who received kidney transplants in the past 10 years at our center. Demographic/ laboratory data, kidney failure etiologies, donor types, and immunosuppressive treatments were recorded. Patients were grouped as those with and without BKV infection, with groups compared in terms of transplant age, sex, kidney failure etiology, donor type, immunosuppressive treatments, presence of ureteral stents, acute rejection episodes, accompanying viral infections, glomerular filtration rate, and graft loss rate., Results: Twelve patients (8.3%) had BK polyomavirus infection. All 12 patients had viruria (8.3%), 8 (5.5%) had viremia, and 4 (2.8%) had BK polyomavirus nephropathy. Two patients (1.4%) had graft loss because of BK polyomavirus nephropathy. When patients with and without infection were compared, no significant differences were found in terms of sex, transplant age, donor type, presence of a ureteral stent, acute rejection, graft loss, or immunosuppressive treatment (P > .05). Rates of congenital anomalies of the kidney and urinary tract were 30.3% and 66.6% in those without and with BK polyomavirus infection, respectively (P < .05). The group positive for BK polyomavirus had a significantly higher incidence of cytomegalovirus infection versus the group without infection (P < .05). Glomerular filtration rate values at years 1 and 3 were similar between groups (P > .05)., Conclusions: Frequency of BK polyomavirus nephropathy in pediatric patients undergoing kidney transplant in our center was consistent with data from other centers. Graft loss can be prevented by early detection and treatment through close periodic control and adequate evaluation of risk factors.

Background: Polyomavirus (PV) infection and PV-associated nephropathy (PVAN) are some of the most important problems in kidney transplantation., Purpose: Our objective was to determine the incidence of PV viruria and PV replication in single-center Polish kidney transplant recipients (KTR)., Methods: Urine samples from 155 cadaveric KTR were analyzed for PV viruria using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The PV replication was recognized when the urine level was >10 7 PV DNA copies/mL of urine., Results: Based on the PV DNA analysis, the patients were divided into 3 groups: Group 1 (n = 87; 56.1%) without viruria, Group 2 (n = 44; 28.4%) with viruria but without PV replication, and Group 3 (n =24; 15.5%) with PV replication. The presence of PV viruria was correlated with the type of immunosuppressive regimen, strongly associated with tacrolimus intake. There was no correlation between viruria and mycophenolate daily dose in the study population. In Group 3 there were 6 patients (3.9%) with high viruria (>10 10 copies/mL), and 5 patients from this group had confirmed PVAN in allograft biopsy., Conclusions: The prevalence of BK virus infection in KTR is similar to that reported in studies from other countries. We confirmed that PV viruria can be both a good screening for PV infection and a good predictor of PVAN. Tacrolimus was the most important predictor of PV viruria and PV replication in KTR., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: BK polyomavirus-associated nephropathy is a troublesome disease caused by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients. There are no effective treatments available, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for identification of patients at high risk of viraemia., Methods: We conducted a retrospective study to assess the correlation between pre-transplantation BKPyV serostatus and post-transplantation incidence of BKPyV infection. Sera from 329 recipients and 222 matched donors were tested for anti-BKPyV antibodies against BKPyV serotypes I and IV by using a virus-like particle-based immunoglobulin G enzyme-linked immunosorbent assay, and BKPyV DNA load was monitored for at least 1 year post-transplantation., Results: Eighty recipients were viruric and 59 recipients were viraemic post-transplantation. In the post-transplantation period, the probability of developing viraemia for serotype I increased from 4.3% for the D-/R+ group to 12.1% for the D+/R+ group, climbing to 37.5% for the D+/R- group (P < 0.05). When calculating recipient mean titres for serotypes I and IV, we observed a clear difference in the proportions of viraemia, decreasing from 50% for mean titres <400 to 13.5% for titres ≥400 (P < 0.001), as well as a higher proportion of presumptive nephropathy (50% versus 23.1%, respectively; P < 0.05). In univariate analysis, this parameter had an odds ratio of 6.41 for the risk of developing post-transplantation BKPyV viraemia (95% confidence interval 3.16-13.07; P < 0.0001)., Conclusions: Determination of both donor and recipient BKPyV seropositivity before transplantation and antibody titre measurements may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Introduction: BK polyomavirus (BKV) is a common infection among kidney transplant recipients (KTR). Risk factors and outcomes based on donor characteristics remain largely unknown., Methods: In this study, we aimed to analyze the impact of donor factors through a paired kidney analysis. We included 289 pairs of adult deceased donor transplants (578 KTRs total); each pair had received kidneys from the same donor. Recipient pairs were divided into three groups: "no BK group" if neither KTR developed BK viremia (n = 336), "discordant" if the only one did (n = 176), and "concordant" if both did (n = 66). Acute rejection (AR), graft failure, and BK nephropathy (BKN) were outcomes of interest., Results: Donors in the concordant group were younger, had lower kidney donor profile index (KDPI), and were less likely to be donor after circulatory death (DCD). In multivariate analyses, KTRs who had a donor with a higher body mass index (BMI) (hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99; p = .009) were less likely to develop BKV. Concordance was not associated with AR (HR: 0.83; 95% CI: 0.51-1.34; p = .45), graft failure (HR: 1.77; 95% CI: 0.42-7.50; p = .43), or BKN (HR: 1.02; 95% CI: 0.51-2.03; p = .96)., Discussion: Our study suggests lower donor BMI is associated with BKV infection, and concordance or discordance between paired kidney recipients is not associated with poor outcomes., (© 2021 Wiley Periodicals LLC.)

Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Immunosuppression following kidney transplantation increases risk of BK polyomavirus reactivation, a common cause of graft dysfunction and failure. Subsequent retransplantation is a viable option that has not been extensively studied. This study further characterizes BK Virus Nephropathy (BKVN) and retransplantation in the most expansive population to date, geographically, temporally, and in magnitude., Materials and Methods: The OPTN/UNOS database was used to identify patients who received kidney or kidney-pancreas transplantation between 1987 and 2018 that resulted in BKVN-attributed failure (n = 1587). This population was divided into those who underwent retransplantation (n = 495) and those who did not (n = 1092)., Results: The retransplanted cohort was younger (45 vs. 53 yr; P<0.0001) and had fewer prior kidney transplants (P<0.003), lower expected post-transplant survival (P<0.001), lower rates of delayed graft function (DGF) (14.1% vs. 22.2%; P=0.0008), a greater proportion of white patients (55.4% vs. 43.2%; P=0.0002), a greater proportion of living donors (35.8% vs. 23.0%; P<0.0001), and longer allograft lifespan (2.95 vs. 2.41 yr; P<0.0001), compared to those not retransplanted. Among retransplants, DGF and high kidney donor profile index (KDPI) were associated with decreased allograft lifespan (P=0.001, P=0.0005, respectively). Steroid induction had no effect on allograft lifespan when compared to steroid-free regimens (P=0.915). Retransplanted allografts lasted longer than previous BKVN-failed grafts (10.44 and 3.70 years, respectively; P<0.0001)., Conclusions: Retransplantation following BKVN-associated graft failure has been associated with favorable outcomes. To maximize allograft lifespan in retransplantation, clinicians may consider selection of low KDPI donors, prevention of delayed graft function, and tailored immunosuppressive regimens that minimize steroids., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Infection with human tumor viruses is one of the hypothesized causes of cancer. The current investigation aimed to explore the presence and quantitative analysis of a new human tumor virus, Merkel cell polyomavirus (MCPyV) in tissue samples of 114 patients with oral cavity lesions including oral squamous cell carcinoma (OSCC), oral lichen planus (OLP), Dysplasia and oral irritation fibroma (OIF) in Northern Iran., Methods: From 114 formalin fixed paraffin embedded samples; 35 with SCC, 29 with OLP, 14 with dysplasia and 36 with OIF were cut, deparaffinized and DNA was extracted. Quantitative detection of MCPyV large T antigen was performed by absolute quantitative Real-Time PCR., Result: MCPyV DNA was detected in 30.6% (n: 11/36) of IF, 24.1% (n; 7/29) of OLP, 21.4% (n:3/14) of dysplasia and 20% (n;7/35) of OSCC samples. The mean MCPyV DNA copy number was 2.32×10-2 ± 3.97 ×10-2, 2.02×10-2 (SD=3.13×10-2), 2.69×10-4 (SD=2.51×10-4), and 2.56×10-4 (SD=6.73×10-4) per cell in OSCC, dysplasia and both of OLP and OIF samples, respectively (P=0.76)., Conclusion: This study provides the first data from Iran regarding the presence of MCPyV genome in oral cavity lesions and oral cancer. These results also emphasize that MCPyV has an active role in the occurrence of oral lesions and progression to cancer. Further studies should be carried out to clarify the role of MCPyV in oral cavity lesions.

Background: BK polyomavirus (BKV) can cause hemorrhagic cystitis (HC) in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). It remains unclear whether nosocomial BKV infections occur. During a 9-month period, an increase in BKV-associated HC (BKV-HC) cases was observed at our institution., Aim: The BKV-HC cluster population was compared with populations of HSCT patients from before and after the BKV-HC cluster to evaluate whether nosocomial BKV transmission had occurred., Methods: A retrospective analysis was carried out to assess the risk of patients developing BKV-HC after HSCT. The background data of the cluster patients were compared with those of the patients who underwent HSCT before or after the cluster, and the collected BKV isolates were serotyped., Results: BKV-HC involving grade ≥2 hematuria occurred in six of 15 HSCT recipients during a 9-month period. The incidence of BKV-HC was significantly higher in this period than in the other periods (p = 0.0014). There were no significant differences in the patients' background data between the cluster and non-cluster periods, including in terms of risk factors for BKV-HC. Serotype analyses of BKV revealed that the BKV detected in the urine samples from four of the six BKV-HC patients belonged to subtype Ic. The gene sequences of these four BKV exhibited >99.5% homology., Conclusion: Our study suggests that nosocomial BKV infections may occur after HSCT. Although many cases of BKV-HC are caused by the reactivation of a latent virus, it is necessary to employ appropriate hygiene measures when cases of BKV-HC occur., (© 2021 Wiley Periodicals LLC.)

Objectives: To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation., Methods: In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed., Results: In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%)., Conclusions: The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy., (© 2021 The Japanese Urological Association.)

JC virus (JCV) causes progressive multifocal leukoencephalopathy in immunocompromised patients. The prevalence and genotype patterns of JCV vary between different geographical regions. This study was done to investigate the prevalence and genotype distribution of JCV in patients with hematological malignancies in Vietnam. A total of 48 urine samples were collected from patients with hematological malignancies. DNA was extracted and detection of JCV was by nested-polymerase chain reaction. Sequence analysis was obtained and a phylogenetic tree was constructed for genotyping of JCV. Twenty-seven (56.25%) urine samples tested positive for JCV. JCV genotype 7 was only observed in this study. Subtype analysis showed that JCV subtype 7A was the most commonly prevalent, followed by 7B1 and 7C1. Other subtypes were not detected in this population. There were no significant differences associated with age, gender, and biochemical parameters between patients with JCV and without JCV excretion in urine. The present study showed a high prevalence of JCV in the urine of patients with hematologic malignancies. The most common genotype found in this population was JCV subtype 7A., (© 2021 Wiley Periodicals LLC.)

Objectives: This study focused on the role that BK polyomavirus (BKPyV) genotypes can play in the development of BKPyV-associated complications in renal transplant recipients., Methods: A retrospective observational study (January 2015 to April 2018) was conducted by analyzing BKPyV genotypes in 180 blood samples with detectable BKPyV viral load (VL) > 1000 copies/mL, from 63 renal transplant recipients. VL and BKPyV genotypes detections were based on real-time PCR (rt-PCR)-specific assays., Results: Forty-four patients (44/63 [69.8%]) were men, and the median age was 55.0 (interquartile range 49.0-66.0 years). Eleven patients had clinical manifestations (11/63 [17.5%]). The most frequently detected genotypes were I (14/63 [22.2%]) and II (13/63 [20.6%]). Half of the patients (33/63 [52.4%]) had a mixed genotype, most with genotypes I and II (25/33 [75.8%]). Patients with infection by mixed genotypes showed VLs that were detected earlier (in the first year after transplantation) than those with a single genotype (25/33 [75.8%] vs 13/30 [43.3%], P = .009) and demonstrated greater risk of developing clinical manifestations associated with BKPyV (odds ratio 12.609, 95% confidence interval 1.503-105.807). Moreover, patients with first BKPyV VL > 10 000 copies/mL more frequently presented mixed genotypes (12/16 [75.0%] vs 21/47 [44.7%], P = .036)., Conclusions: The probability of developing clinical manifestations is higher in infections by mixed genotypes. Therefore, the detection of BKPyV genotypes by rt-PCR can provide relevant information to stratify patients' risk of BKPyV-associated complications and guide the clinical management of BKPyV infection in kidney transplant recipients., (© 2021 Wiley Periodicals LLC.)

The members of the viral family Polyomavirae are widespread in the human population. According to serological studies, almost all adults are infected with at least one of this group of viruses. The primary infection usually occurs in childhood without any clinical signs, and after the primary infection, the viruses establish a persistent infection accompanied by occasional reactivation and shedding of the virus. These viruses often reactivate in immunosuppressed individuals, but only in a minority of these patients, the reactivation results in disease development. This biological property of human polyomaviruses makes laboratory diagnosis considerably difficult. The paper provides an overview of methods for diagnosing human polyomaviruses, which are commonly used for screening, and methods that are still validated by research but have the potential to improve detection and to identify patients at risk of developing diseases associated with polyomavirus infection.

Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for the global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission-dynamic model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV infections are persistent in the MSM population, with sustained circulation of the virus among unvaccinated individuals. Coverage around 75% of both sexes would be necessary to eliminate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between a vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV elimination may be achieved if men's coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.

Background and Objectives: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients., Design, Setting, Participants, & Measurements: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database., Results: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95)., Conclusions: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021&#95;03&#95;10&#95;CJN18101120&#95;final.mp3., (Copyright © 2021 by the American Society of Nephrology.)

Myxomatosis is an infectious disease caused by the myxoma virus (MYXV), which has very high mortality rates in European wild rabbits (Oryctolagus cuniculus). While sporadic cases of myxomatosis have also been reported in some hare species, these lagomorphs are considered to have a low susceptibility to MYXV infection. In the present study, we describe the spatiotemporal evolution and main epidemiological findings of novel hare MYXV (ha-MYXV or MYXV-Tol) epidemics in Iberian hares (Lepus granatensis) in Spain. In the period 2018-2020, a total of 487 hares from 372 affected areas were confirmed to be MYXV-infected by PCR. ha-MYXV outbreaks were detected in most of the Spanish regions where the Iberian hare is present. The spatial distribution was not homogeneous, with most outbreaks concentrated in the southern and central parts of Spain. Consecutive outbreaks reported in the last two years suggest endemic circulation in Spain of this emerging virus. A retrospective study carried out just after the first epidemic period (2018-2019) revealed that the virus could have been circulating since June 2018. The number of outbreaks started to rise in July, peaked during the first half of August and October and then decreased sharply until January 2019. The apparent mean mortality rate was 55.4% (median: 70%). The results indicated high susceptibility of the Iberian hare to ha-MYXV infection, but apparent resistance in the sympatric hare species present in Spain and less infectivity in European rabbits. The novel ha-MYXV has had significant consequences on the health status of Iberian hare populations in Spain, which is of animal health and conservation concern. The present study contributes to a better understanding of ha-MYXV emergence and will provide valuable information for the development of control strategies. Further research is warranted to assess the impact of this emerging virus on wild lagomorph populations and to elucidate its ecological implications for Iberian Mediterranean ecosystems., (© 2020 Wiley-VCH GmbH.)

Background: BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after hematopoietic stem cell transplantation (HSCT)., Methods: A retrospective review was performed to determine the frequency of BKV-HC and identify risk factors and renal morbidity associated with BKV-HC in pediatric HSCT recipients at our institution., Results: A total of 314 pediatric recipients underwent allogeneic HSCT for either malignant (173, 55.1%) or nonmalignant disorders (141, 44.9%) from January 1, 2011, to December 31, 2015, with a minimum follow-up of 5 years post-HSCT. Severe BKV-HC (grades 3 and 4) was prevalent in 46 out of 67 (68.7%) recipients. Timing to presentation of severe BKV-HC (grades 3 and 4) occurred at a median of 37 days (26, 74; IQ1, IQ3) post-HSCT, with the duration of macroscopic hematuria lasting a median of 37.5 days (18, 71; IQ1, IQ3). In the first 60 days post-HSCT, peak acute kidney injury (AKI) stages 2 and 3 were seen more frequently in HSCT recipients who developed BKV-HC than those without (P = .004). Similarly, during post-HSCT days 61 to 100, peak AKI stage 3 was also more frequently seen in HSCT recipients who already developed BKV-HC prior to or during this time period than those without BKV-HC (P = .0002). Recipients who developed BKV-HC within 1 year of HSCT had more frequent mild to moderate chronic kidney disease (CKD stages 2-3) than those without BKV-HC (P = .002 and .007, respectively). On multivariate analysis, BKV-HC was associated with all-cause mortality (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.35-3.65). The following clinical variables were associated with time to development of HC on multivariate analysis: age (subdistribution HR [sHR] 1.11; 95% CI: 1.06-1.16) and myeloabalative conditioning regimen (sHR 4.2; 95% CI: 2.12-8.34)., Conclusions: Pediatric HSCT patients with BKV-HC experience significant morbidity and mortality. Renal morbidity, including AKI and CKD, is associated with BKV-HC., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up)., Methods: We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive)., Results: At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status., Conclusions: Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in cats with infection in its progressive form. Although there are numerous reports on the occurrence of FeLV in the feline population worldwide, there is a paucity of data in Asia. In this study, we assessed the circulation of FeLV by ELISA and nested PCR in cats from different countries in Southeast Asia (i.e., Thailand, Malaysia, Singapore, Philippines, Indonesia and Vietnam) and Taiwan during 2017-2018. Forty-seven cats were positive to FeLV by antigen or provirus detection, but 32 samples were considered truly positive on the basis of positive molecular testing. Frequency of occurrence of FeLV proviral DNA ranged from 0% (0/43 positive samples) in Indonesia to 18.5% (22/119 positive samples) in Thailand. A statistically significant association (p < 0.05) was found between country of cats origin, age, lifestyle, abnormal oral mucosa, and FeLV molecular positive results. In-depth studies are needed in other countries in Southeast Asia to elucidate the mosaic of knowledge about FeLV epidemiology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intrapatient variability (IPV) in tacrolimus has been increasingly acknowledged as a risk factor for poor graft survival after kidney transplantation. Although past studies have mainly accounted for IPV in acute or chronic rejection states as due to underimmunosuppression, this is not yet clear. So far, tacrolimus IPV for BK virus-associated nephropathy (BKVN) and chronic calcineurin inhibitor toxicity (CNIT) has not been investigated. Here, we evaluated IPV in tacrolimus for BKVN and chronic CNIT, which are mainly considered as overimmunosuppression states. In this case-control study, kidney allograft biopsies conducted between 1998 and 2018 were included, with patients grouped by biopsy results as BKVN alone group, CNIT alone group, and normal graft function (control group). IPV was estimated as mean absolute deviation. Our study groups included 25 kidney transplant recipients with BKVN alone, 91 patients with CNIT alone, and 60 patients with normal 5-year graft survival (control group). In analyses of IPV in tacrolimus six months before graft biopsy, IPV was highest in the BKVN group (P = 0.001). The BKVN group also had the highest IPV in tacrolimus at 12 months after biopsy (P = 0.001), with all pairwise comparisons statistically different between groups. At 12 months after biopsy, five patients (20%) in the BKVN group and 10 patients (10.9%) in the CNIT group had graft loss. Among other risk factors, BKVN and chronic CNIT are consequences related to high IPV. Quantification of IVP for tacrolimus in clinical practice would help to optimize kidney transplant outcomes.

Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.

Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case-control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4 + T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. SIGNIFICANCE: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer., (©2020 American Association for Cancer Research.)

Background: Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection in immunodeficient patients., Objective: The aim of the study was to evaluate the prevalence of BKV and JCV in immunocompetent individuals in the north of Iran., Methods: Ninety-one urine samples were obtained from renal transplant recipients with a mean age of 39.78 ± 11.19 years. A healthy control group of 65 volunteers with an average age of 40.32 ± 10.7 years also contributed. After DNA extraction, positive cases were detected through PCR. Genotyping was done by alignment and phylogenetic tree construction of the VP1 region against all known JCV and BKV genotypes., Results: The prevalence of BKV and JCV was 15.38 and 19.78%, respectively. JCV was detected in 7.69% of the control group. The prevalence of the BKV between the case and control groups was significant (p < 0.0001). There was no significant association between BKV and JCV and duration of dialysis (p > 0.05). Overall, 62.16% of JCV cases were genotype I. Besides, genotype II was dominant within patients with BKV-positive patients., Discussion: The results obtained here show a relatively lower prevalence of BKV and JCV in immunocompromised renal transplant receivers and healthy control than those reported from other areas in Iran. JCV genotyping was evaluated for the first time in Iran. Genotype I for JCV and genotype II for BKV were dominant genotypes in the north of Iran., (© 2021 S. Karger AG, Basel.)

Both reticuloendotheliosis and Marek's disease are neoplastic diseases of chickens caused by reticuloendotheliosis virus (REV) and Marek's disease virus (MDV), respectively. The infection of REV or MDV may lead to clinical tumors and also result in immunosuppression and easily allow secondary infection by other pathogens. Here, we investigated a breeder flock of three-yellow chickens in southern China that had been vaccinated with CVI988/Rispens at hatching and had experienced depression, weakness, reduction in weight gain, and an increased death rate after 120 d of age. The morbidity and mortality were 20% and 10%, respectively, at 140 d of age when this infection was diagnosed. The necropsy of the birds revealed significant tumor-like lesions in the heart, liver, spleen, and ceca. Peripheral blood lymphocytes and tumor-like tissues were sampled for PCR detection and for histopathological observation, for virus isolation and the subsequent immunofluorescent assay on the cell cultures and for gene sequencing of the isolated viruses. A REV isolate GX18NNR1 and a MDV isolate GX18NNM5 were both recovered from the sampled bird. Further phylogenetic analysis based on the env gene of REV and the meq gene of MDV demonstrated that GX18NNR1 was closely related to the reference REV strain MD-2, which was isolated from a contaminated commercial turkey herpesvirus vaccine. In addition, the GX18NNM5 was found to belong to the Chinese very virulent MDV strains' cluster. The coinfection of REV and MDV may contribute to tumor outbreaks with high morbidity and mortality in three-yellow chicken flocks., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To compare the infection of BK virus in the recipients of living donor(LD) kidney transplant and deceased donor(DD) kidney transplant. Methods: A total of 911 recipients who underwent kidney transplantation in the Organ Transplantation Research Institute of the 8th Medical Center of the People's Liberation Army General Hospital from January 2015 to August 2019 were enrolled in this study. The DNA copies of BK virus in urine and peripheral blood of kidney transplant recipients were detected by real-time quantitative PCR. The patients were divided into LD group ( n= 255) and DD group ( n= 656). BK virus infection in recipients with DD kidney transplant were compared with that in recipients of LD kidney transplant. Results: The BK virus positive rate in the urine of all subjects was 13.06%(119/911), and that in blood was 2.96% (27/911). The positive rate of BK virus in urine after kidney transplantation was significantly higher than that in blood( P< 0.000 1). The positive rate in urine was 9.02% (23/255) in LD group, which was significantly lower than that of 14.63% (96/656) in DD group in the same period (χ(2)=5.097, P= 0.012); The positive rate of BK virus infection in relatives group was 0.78% (2/255), which was significantly lower than that of 3.81% (25/656) in DD group (χ(2)=5.849, P= 0.007). Conclusions: There was a significant difference in the infection rate of BK virus between the LD and DD group. The incidence of BK virus infection in kidney transplant recipients from DD was higher than that of from LD kidney transplant recipients.