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Human T‐lymphotropic virus type‐1 (HTLV‐1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T‐cell leukaemia/lymphoma malignancy and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro‐myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV‐1‐associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV‐1‐infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV‐1 a natural probe for the study of malignancy and neuro‐inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV‐1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro‐inflammatory propensity of HTLV‐1‐induced HAM/TSP. Such an emphasis on the virus‐host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV‐1 therapeutics. [ABSTRACT FROM AUTHOR]

Introduction: In acute conditions, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes multi‐organ damage due to the induction of inappropriate immune responses, particularly lung tissue fibrosis. To evaluate the consequence of the deterioration of the immune system, autoimmune markers were assessed. Method s : In a case–control study, 108 patients with coronavirus disease 2019 (COVID‐19) were admitted to the intensive care unit (ICU), and 158 outpatients with mild clinical symptoms, with SARS‐CoV‐2 reverse transcription quantitative polymerase chain reaction (RT‐qPCR) positive tests, were included for comparison. The demographic and hematologic variables and presence of the main autoantibodies in sera of 40 eligible ICU‐hospitalized COVID‐19 patients and 40 COVID‐19 outpatients were assessed. Out of 108 COVID‐19 ICU‐hospitalized patients, 40 were selected as the control group (40/158) who had no underlying diseases before hospitalization, according to their self‐declaration and clinical records at the time of admission. Results: The results demonstrated that the main complete blood count indices, such as red blood cells and platelets, decreased dramatically in ICU‐hospitalized patients. Furthermore, the autoantibody profiles were positive in 45% and 15% of ICU‐admitted patients for antinuclear antibodies and antineutrophilic cytoplasmic autoantibodies, respectively. In ICU patients, anti‐PM/Scl 100 or AMA‐M2 was 33%. Anti SS‐A, anti‐SS‐B, anti‐Ro‐52, and anti‐Jo‐1 in 11.5% for each one were reactive. Other autoantibodies of the ICU group were as follows: CENP (5.6%), Rib‐protein (5.6%), and nucleosome (5.6%). However, only two individuals in the control group had positive results for SS‐A and SS‐B (5%). Conclusion: Induction of such particular autoantibodies by the virus can justify the multi‐organ involvement and severity of the disease in ICU patients, which may also cause other organ involvement in the long term. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T lymphocytes caused by human T lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 was brought to the World Health Organization (WHO) and researchers to address its impact on global public health, oncogenicity, and deterioration of the host immune system toward autoimmunity. In a minority of the infected population (3–5%), it can induce inflammatory networks toward HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or hijacking the infected CD4+ T lymphocytes into T regulatory subpopulation, stimulating anti-inflammatory signaling networks, and prompting ATLL development. This review critically discusses the complex signaling networks in ATLL pathogenesis during virus–host interactions for better interpretation of oncogenicity and introduces the main candidates in the pathogenesis of ATLL. At least two viral factors, HTLV-1 trans-activator protein (TAX) and HTLV-1 basic leucine zipper factor (HBZ), are implicated in ATLL manifestation, interacting with host responses and deregulating cell signaling in favor of infected cell survival and virus dissemination. Such molecules can be used as potential novel biomarkers for ATLL prognosis or targets for therapy. Moreover, the challenging aspects of HTLV-1 oncogenesis introduced in this review could open new venues for further studies on acute leukemia pathogenesis. These features can aid in the discovery of effective immunotherapies when reversing the gene expression profile toward appropriate immune responses gradually becomes attainable. [ABSTRACT FROM AUTHOR]

Objective(s): Human T leukemia virus type one (HTLV-1) causes two life-threatening diseases in around five percent of infected subjects, a T cell malignancy and a neurodegenerative disease. TAX and HBZ are the main virulence agents implicated in the manifestation of HTLV-1-associated diseases. Therefore, this study aims to produce these HTLV-1 factors as recombinant Fc fusion proteins to study the structures, their immunogenic properties as vaccines, and their capability to produce specific neutralization antibodies. Materials and Methods: TAX and HBZ sequences were chosen from the NCBI-nucleotide database, then designed as human Fc chimers and cloned into Pichia pastoris. Produced proteins were purified by HiTrap affinity chromatography and subcutaneously injected into rabbits. Rabbit Abs were purified by batch chromatography, and their neutralization activities for the HTLV-1-infected MT-2 cell line were assessed. Furthermore, the protective abilities of recombinant proteins were evaluated in Tax or HBZ immunized rabbits by MT-2 cell line inoculation and measurement of HTLV-1-proviral load. Results: Specific Abs against Tax and HBZ can eliminate 2 million MT-2 cells in 1/1000 dilution in vitro. In challenging assays, the immunization of the animals using Tax or HBZ had no protective activity as HTLV-1 PVL was still positive. Conclusion: The result suggests that recombinant TAX and HBZ: hFcγ1 proteins can produce a proper humoral immune response. Therefore, they could be considered a passive immunotherapy source for HTLV-1-associated diseases, while total TAX and HBZ proteins are unsuitable as HTLV-1 vaccine candidates. [ABSTRACT FROM AUTHOR]

Objective(s): Despite advances in the treatment of adult T-cell leukemia/lymphoma (ATLL), the survival rate of this malignancy remains significantly low. Auraptene (AUR) is a natural coumarin with broad-spectrum anticancer activities. To introduce a more effective therapeutic strategy for ATLL, we investigated the combinatorial effects of AUR and arsenic trioxide (ATO) on MT-2 cells. Materials and Methods: The cells were treated with different concentrations of AUR for 24, 48, and 72 hr, and viability was measured by alamarBlue assay. Then, the combination of AUR (20 µg/ml) and ATO (3 µg/ml) was administrated and the cell cycle was analyzed by PI staining followed by flow cytometry analysis. In addition, the expression of NF-κB (REL-A), CD44, c-MYC, and BMI-1 was evaluated via qPCR. Results: Assessment of cell viability revealed increased toxicity of AUR and ATO when used in combination. Our findings were confirmed by accumulation of cells in the sub G1 phase of the cell cycle and significant down-regulation of NF-κB (REL-A), CD44, c-MYC, and BMI-1. Conclusion: Obtained findings suggest that combinatorial use of AUR and ATO could be considered for designing novel chemotherapy regimens for ATLL. [ABSTRACT FROM AUTHOR]

Summary: Human T lymphotropic virus type‐1 (HTLV‐1) is a well‐known human oncovirus, associated with two life‐threatening diseases, adult T cell leukaemia/lymphoma (ATL) and HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The study of this oncogenic virus is significant from two different aspects. First, HTLV‐1 can be considered as a neglected public health problem, which may spread slowly worldwide. Second, the incidence of HTLV‐1 associated diseases due to oncogenic effects and deterioration of the immune system towards autoimmune diseases are not fully understood. Furthermore, knowledge about viral routes of transmission is important for considering potential interventions, treatments or vaccines in endemic regions. In this review, novel characteristics of HTLV‐1, such as the unusual infectivity of virions through the virological synapse, are discussed in the context of the HTLV‐1 associated diseases (ATL and HAM/TSP). [ABSTRACT FROM AUTHOR]

Interleukin (IL)-12, IL-18, and interferon gamma (IFN-γ) can induce Th1-inflammatory responses in favor of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) manifestation. In this study, the gene expression and plasma levels of these cytokines were evaluated. The peripheral blood mononuclear cells (PBMCs) in 20 HAM/TSP patients, 21 asymptomatic carriers (ACs), and 21 healthy subjects (HSs) were assessed for the expression of IL-18, IL-12, and IFN-γ, using qRT-PCR. The plasma level of IL-18 and IFN-γ were measured by an ELISA method. The mean of HTLV-1 proviral load (PVL) in the HAM/TSPs was 1846.59 ± 273.25 and higher than ACs at 719.58 ± 150.72 (p = 0.001). The IL-12 was considerably expressed only in nine ACs, five HAM/TSPs, and all HSs. Furthermore, the gene expression and plasma levels of IL-18 were lower in the HTLV-1-positive group than the control group (p = 0.001 and 0.012, respectively); however, there was no significant difference between the ACs and HAM/TSPs. The IFN-γ level was higher in the HTLV-1-positive group (p < 0.001) than HSs. Although there were no correlation between plasma levels of IL-18 and IFN-γ with PVL in the ACs, a positive correlation was observed between plasma IL-18 levels and PVL (r = 0.654, p = 0.002). The highest levels of IFN-γ were observed in the HAM/TSPs which has a significant correlation with HTLV-1-HBZ (r = 0.387, p = 0.05) but not with Tax. However, no significant correlation was found between PVL and proinflammatory pattern. Apart from the IFN-γ as a lymphokine, as a host factor, and HTLV-1-HBZ, as a viral agent, the other proinflammatory monokines or HTLV-1 factors are among the less-effective agents in the maintenance of HAM/TSP. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen (HBsAg). This study aimed to determine seropositivity for antibodies against HBV core antigen (anti-HBc) and the frequency of OBI among the HBsAg non-reactive blood donors in Mashhad, northeastern Iran. Methods: In this cross-sectional study, serum samples of HBsAg-negative blood donors were examined for anti-HBc during June and August 2018. Anti-HBc-positive samples were tested for antibodies against HBsAg (anti-HBs), and those with negative results were classified as isolated anti-HBc cases. The presence of HBV DNA in the C, S, and X gene regions was assessed by a qualitative real-time polymerase chain reaction method in all HBsAg-negative samples. OBI subjects were detected by the presence of at least one HBV genomic region. Results: Of 540 HBsAg-negative donors, 29 (5.4%; 95% confidence interval: 3.6--7.6%) showed seroreactivity for anti-HBc, of whom 18 individuals were also seropositive for anti-HBs. All donors showed negative results for all three HBV genes regardless of their serum anti-HBc status. Conclusion: Based on our findings, we suggest routine screening of Iranian blood donation volunteers for serum anti-HBc and anti-HBs but not HBV DNA. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross‐sectional study, blood samples were taken from 249 recently diagnosed HCV‐infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV‐RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut‐off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV‐RNA load. Regression model: log viral load = 7.69 − 1.01 × G3 − 0.7 × G1 + 0.002 × ALT − 0.86 × fatigue. [ABSTRACT FROM AUTHOR]

Background: Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder of HTLV-1-host interactions in infected TCD4+ cells. In this study, the HTLV-1 proviral load (PVL) and HBZ as viral elements and AKT1, BAD, FOXP3, RORγt and IFNλ3 as the host factors were investigated.Methods: The study was conducted in ATLLs, HTLV-1-associated myelopathy/tropical spastic paraparesis patients (HAM/TSPs) and HTLV-1-asympthomatic carriers (ACs). The DNA and mRNA from peripheral blood mononuclear cells were extracted for gene expression assessments via qRT-PCR, TaqMan assay, and then confirmed by western blotting.Results: As it was expected, the HTLV-1-PVL were higher in ATLLs than ACs (P = 0.002) and HAM/TSP (P = 0.041). The HBZ expression in ATLL (101.76 ± 61.3) was radically higher than in ACs (0.12 ± 0.05) and HAM/TSP (0.01 ± 0.1) (P = 0.001). Furthermore, the AKT1 expression in ATLLs (13.52 ± 4.78) was higher than ACs (1.17 ± 0.27) (P = 0.05) and HAM/TSPs (0.72 ± 0.49) (P = 0.008). However, BAD expression in ATLL was slightly higher than ACs and HAM/TSPs and not significant. The FOXP3 in ATLLs (41.02 ± 24.2) was more than ACs (1.44 ± 1) (P = 0.007) and HAM/TSP (0.45 ± 0.15) (P = 0.01). However, RORγt in ATLLs (27.43 ± 14.8) was higher than ACs (1.05 ± 0.32) (P = 0.02) but not HAM/TSPs. Finally, the IFNλ3 expression between ATLLs (31.92 ± 26.02) and ACs (1.46 ± 0.63) (P = 0.01) and ACs and HAM/TSPs (680.62 ± 674.6) (P = 0.02) were statistically different, but not between ATLLs and HAM/TSPs.Conclusions: The present and our previous study demonstrated that HTLV-1-PVL and HBZ and host AKT1 and Rad 51 are novel candidates for molecular targeting therapy of ATLL. However, high level of RORγt may inhibit Th1 response and complicated in ATLL progressions. [ABSTRACT FROM AUTHOR]

Viral hepatitis is considered as a worldwide health problem and hepatitis B virus (HBV) infection is one of the major health concerns which are annually responsible for more than one million deaths. HBV can be classified into at least eight genotypes, A–H and four major subtypes. Predominant HBV genotype in Mediterranean and Middle East countries is genotype D, but there is a few studies have been performed on the HBV genotype in Iran. The genotype characteristic and phylogenetic analyses were determined in chronic HBV patients in the northeast of Iran. First, seventy-eight patients with chronic HBV infection were enrolled. Demographic features were reviewed and sera samples were collected. HBV genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and results were confirmed by sequencing. Finally, a phylogenetic tree was obtained using Geneious software. Sixty-two (79.48%) of patients were males (mean age: 36.82 years). Twelve out of 78 patients (15.4%) were hepatitis B envelope antigen (HBeAg)-reactive. There were no significant differences between the clinical and HBeAg-positive serological data and HBeAb positive individuals. RFLP DNA sequencing and phylogenetic analysis showed that genotype D was the only genotype which observed in Mashhad, northeast of Iran. This is the first report of HBV genotyping in Mashhad. The results revealed that genotype D was the only genotype detected in this area which was consistence with previous studies in the Middle East, Mediterranean countries, southwest and center of Iran. [ABSTRACT FROM AUTHOR]

Objective(s): Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fcdomain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB. Materials and Methods: The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris. To evaluate the expression of recombinant proteins, SDS-PAGE and immunoblotting were used. The immunogenicity of recombinant proteins, with and without BCG were assessed in BALB/c mice and specific cytokines against recombinant proteins (IFN-γ, IL-12, IL-4, IL-17 and TGF-β) were evaluated. Results: The levels of IFN-γ and IL-12 in mice that received recombinant proteins was higher than the control groups (BCG and PBS). Thus, both recombinant proteins (CFP-10:Fcγ2a and CFP-10:His) could excite good response in Th1-cells. The Fc-tagged protein had a stronger Th1 response with low levels of IL-4, as compared to CFP-10:His. However, the highest level of Th1 response was observed in groups that were vaccinated with BCG (prime) and then received recombinant protein CFP-10: Fcγ2a (booster). Conclusion: The results demonstrated that binding mice Fc-domain to CFP-10 protein can increase the immunogenicity of the subunit vaccine. Further studies, might be able to design and produce a new generation of subunit vaccines based on the Fc-fused immunogen. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a major health problem worldwide. Currently, the Bacilli Calmette-Guérin (BCG) is the only available licensed TB vaccine, which has low efficacy in protection against adult pulmonary TB. Therefore, the development of a safe and effective vaccine against TB needs global attention. In the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (CFP-10) and heat shock protein X (HspX) of Mycobacterium tuberculosis fused to the Fc domain of mouse IgG2a as a selective delivery system for antigen-presenting cells (APCs) was produced and its immunogenicity assessed. The optimized gene constructs were introduced into pPICZαA expression vectors, and the resultant plasmids (pPICZαA-CFP-10:Hspx:Fcγ2a and pPICZαA-CFP-10:Hspx:His) were transferred into Pichia pastoris by electroporation. The identification of both purified recombinant fusion proteins was evaluated by SDS-PAGE and immunoblotting. Then the immunogenicity of the recombinant proteins with and without BCG was evaluated in BALB/c mice by assessing the level of IFN-γ, IL-12, IL-4, IL-17 and TGF-β cytokines. Both multi-stage vaccines (CFP-10:HspX:Fcγ2a and CFP-10:HspX:His) induced Th1-type cellular responses by producing high level of IFN-γ (272 pg/mL, p < 0.001) and IL-12 (191 pg/mL, p < 0.001). However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low level of IL-4 (10 pg/mL) compared to the CFP-10:HspX:His group. The production of IFN-γ to CFP-10:HspX:Fcγ2a was markedly consistent and showed an increasing trend for IL-12 compared with the BCG or CFP-10:HspX:His primed and boosted groups. Findings revealed that CFP-10:Hspx:Fcγ2a fusion protein can elicit strong Th1 antigen-specific immune responses in favor of protective immunity in mice and could provide new insight for introducing an effective multi-stage subunit vaccine against TB. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C virus (HCV) infection affects 58 million people globally. The frequency of HCV infection in the general Iranian population is less than 0.5%; however, a concentrated epidemic was reported among people who use drugs, particularly those with a history of drug injection. Objectives: This cross-sectional study was performed to assess the prevalence of HCV infection among high-risk groups outside of prison in northeastern Iran. Methods: A total of 962 participants in Razavi Khorasan province were enrolled from 2018 to 2022. They included drug users referred to drug treatment and harm reduction centers and individuals with a history of crimes such as drug use or imprisonment who worked in a private industrial unit. Serum anti-HCV antibodies were assessed using a rapid or ELISA kit, and seroreactive samples were confirmed by single-step reverse transcriptase or qualitative real-time polymerase chain reactions. A P-value < 0.05 was considered statistically significant. Results: The mean age of 707 males and 255 females was 39.8 ± 10.2 years. Anti-HCV antibodies were detected from 129 samples (13.41%), of which 107 were available for polymerase chain reaction testing. HCV RNA was detected in 88 cases (75.2%); the total viremia rate was calculated as 9.26% (88/950). Logistic regression analysis revealed that HCV infection among drug users was significantly associated with older age (P = 0.002), being single (P = 0.009), and history of drug injection (P < 0.001) or incarceration (P = 0.04). Conclusions: The findings showed a considerably high prevalence of HCV infection among people who use drugs in northeastern Iran. To achieve the global goal of viral hepatitis elimination by 2030, we strongly recommend stricter screening and treatment of this infection among such hard-to-access populations in Iran. [ABSTRACT FROM AUTHOR]

Background: Blood-borne viruses (BBVs) are one of the most important public health concerns. South Khorasan has a long border with Afghanistan and concern has risen there about blood-borne oncogenic viral infections. The aim of the present study was to evaluate the prevalence and associated risk factors of human T-lymphotropic virus 1 (HTLV-1) and co-infections of BBVs in Birjand, Iran's eastern border. Methods: In this cross-sectional study, 3441 subjects were tested for sero-prevalence of HTLV-1 by ELISA. The data on demographic features, HTLV-1-related risk factors and other characteristics of the population were analyzed by Pearson chi-square and logistic regression tests. Finally, the co-infection of BBVs was evaluated in the study. Results: The prevalence of HTLV-1 was 0.3% (95% CI: 0.12-0.48). Notably, the sero-prevalence of HIV, hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV) in our previous studies was reported at 0%, 0.2%, 1.2% and 1.6%, respectively. The results indicated that the occurrence of HTLV-1 infection was associated only with the history of hospitalization (odds ratio [OR]: 0.27, 95% CI: 0.07-0.97, with P = 0.04). The co-infection of HBV with HCV was the most common (2.35%), while a coinfection rate of 1.17% was found for both HBV/HTLV-1 and HBV/HDV. Conclusion: Although a higher prevalence of the viruses was expected, it was close to the overall Iranian population. With respect to close relationship with an HTLV-1 endemic area (Mashhad and Neyshabour), the prevalence is very low; however, more attention is needed. Our findings reinforce the importance of increasing knowledge about BBV-related health risk behaviors to prevent the emergence of new cases, especially in low-risk populations. [ABSTRACT FROM AUTHOR]

There is an urgent need to find an effective therapy for life-threatening HTLV-1-associated diseases. Bitter melon (Momordica charantia) is considered a traditional herb with antiviral and anticancer properties and was tested in this study on HTLV-1 infectivity. GC–MS analyzed the alcoholic extract. In vitro assay was carried out using transfection of HUVEC cells by HTLV-1-MT2 cell line. The cells were exposed to alcoholic and aqueous extracts at 5,10, and 20 µg/mL concentrations. In vivo, mice were divided into four groups. Three groups were treated with HTLV-1-MT-2 cells as test groups and positive control, and PBS as the negative control group in the presence and absence of M. charantia extracts. Peripheral blood mononuclear cells (PBMCs), mesenteric lymph nodes (MLNs), and splenocytes were collected for HTLV-1-proviral load (PVL) assessment, TaqMan-qPCR. The GC–MS analysis revealed 36 components in M. charantia. The studies showed significant reductions in HTLV-1-PVL in the presence of extract in the HUVEC-treated groups (P = 0.001). Furthermore, the inhibitory effects of extracts on HTLV-1 infected mice showed significant differences in HTLV-1-PVL among M. charantia treated groups with untreated (P = 0.001). The T-cells in MLNs were significantly more susceptible to HTLV-1 than others (P = 0.001). There were significant differences among HTLV-1-infected cells in MLNs and splenocytes (P = 0.001 and 0.046, respectively). Also, aqueous and alcoholic extract-treated groups significantly affected HTLV-1-infected PBMCs (P = 0.002 and 0.009, respectively). M. charantia may have effective antiviral properties. The substantial compound of M. charantia could have inhibitory effects on the proliferation and transmission of HTLV-1 oncovirus. [ABSTRACT FROM AUTHOR]

• ATLL malignancy and EBL oncogenesis pathways were investigated. • The RNA-seq, system biology analysis and gene expression assays were compared. • BLV-AS-1–2 in EBL and HTLV-1- HBZ have pivotal roles in the ATLL progression. • HTLV-1-PVL, Tax, and HBZ, the immunological and host-cell factors were evaluated. • HTLV-1-HBZ, the host PI3K/Akt pathway, BCAs, and RAD51 are influential targets. The outcome of successful infection, including human T -cell leukemia virus type 1 (HTLV-1), is determined by the interactions between the host and the infectious agent. Ten years of work on HTLV-1-associated diseases in an endemic region of Iran have been critically compared in the present study. The outstanding findings of RNA-seq, system biology analysis, and gene expression measurements on adult T -cell leukemia/lymphoma (ATLL) and enzootic bovine leukosis (EBL) in our lab encouraged us to investigate the significant role of oncogenes in the ATLL malignancy. Most studies assessed such interactions by the proviral load (PVL), Tax, and HBZ regulatory proteins in HTLV-1 and the host's immunological and cell cycle factors. The current study is a comprehensive comparing view of our previously published and unpublished results investigating the HTLV-1-host interactions leading to the transformation of the infected cell. The main focus has been on the essential proteins implicated in the virus dissemination, cell survival, and proliferation of infected cells toward leukemia development and progression. Similar to its homolog BLV-AS-1–2 in EBL, the HTLV-1- HBZ is a pivotal factor in the maintenance and progression of the ATLL. In addition, the inappropriate activities of the PI3K/Akt pathway, BRCAs, and RAD51 in the DNA repair system, which are orchestrating many other immortalization pathways, might be the central factors in the manifestation of ATLL. HTLV-1- HBZ and the host PI3K/Akt pathway, BCAs , and RAD51 could be suggested as influential targets for the prognosis and proper therapy of ATLL. [ABSTRACT FROM AUTHOR]

One third of the world population has a history of exposure to the hepatitis B virus (HBV), and two billion people are infected with latent tuberculosis (TB). Occult hepatitis B infection (OBI) is defined as the presence of replicative-competent HBV DNA in the liver with detectable or undetectable HBV DNA in the serum of individuals testing negative for the HBV surface antigen (HBsAg). Screening with HBV DNA could identify OBI and significantly reduce carriers and complications of chronic hepatitis B (CHB). This study aims to assess HBV serological markers and OBI molecular diagnosis among people with TB in Mashhad, northeastern Iran. We have performed HBV serological markers (HBsAg, HBc antibodies (Ab) and HBs Ab) in 175 participants. Fourteen HBsAg + sera were excluded for further analysis. The presence of HBV DNA ( C , S , and X gene regions) was assessed by the qualitative real-time PCR (qPCR) method. Frequencies of HBsAg, HBc, and HBs Ab were 8% (14/175), 36.6% (64/175), and 49.1% (86/175), respectively. Among these 42.9% (69/161) were negative for all HBV serological markers. The S , C , and X gene regions were positive in 10.3% (16/156), 15.4% (24/156), and 22.4% (35/156) of participants, respectively. The total OBI frequency was estimated at 33.3% (52/156) when based on detecting one HBV genomic region. Twenty-two and 30 participants had a seronegative and seropositive OBI, respectively. Thorough screening of high-risk groups with reliable and sensitive molecular methods could lead to OBI identification and decrease CHB long-term complications. Mass immunization remains critical in preventing, reducing, and potentially eliminating HBV complications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with two life-threatening diseases; HAM/TSP and ATLL. Due to the slow-growing HTLV-1 infection worldwide, WHO urged for elimination. A large border with Afghanistan, northeast Iran is an endemic region for HTLV-1 infection. Historically, Afghanistan has common sociocultural similarities to Persian peoples. This study was conducted to evaluate HTLV-1 prevalence in Afghan refugees. Also, the HTLV-1 transmission rate and understanding of whether or not the Silk Road has been the route of HTLV-1 infection to Iran were investigated. This case-control study was conducted in a rural area of Fariman city, with Afghan residents who migrated around 165 years ago, from 1857, the Treaty of Paris at the end of the Anglo-Persian war, and a refugee camp in Torbat-e-Jam city. These populations in HTLV-1 endemic area were compared to a segregated population of Afghan refugees in Semnan, the centre of Iran. Blood samples of 983 volunteers were assessed with the ELISA method for the presence of HTLV-1 antibodies and then confirmed by PCR technique. All samples from Afghan refugee camps, Semnan and Torbat-e-Jam, were negative for HTLV-1 infection. However, the prevalence of HTLV-1 infection in Fariman, a rural population of Afghan origin, was approximately 2.73%. The results showed that HTLV-1 is not endemic in Afghanistan, a war-stricken region with refugees distributed worldwide. The land Silk Road has not been the route of HTLV-1 transmission to Northeastern Iran. Importantly, HTLV-1 endemicity might occur during a long time of living in an endemic area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mahdifar 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.)

Objectives: The emergence and spread of multidrug-resistant (MDR) Acinetobacter baumannii isolates is now frequently associated with nosocomial infections. The aim of this study was to evaluate the genetic relatedness and patterns of antimicrobial resistance amongst A. baumannii isolated from a burn centre at a teaching hospital in Iran., Methods: A total of 54 A. baumannii isolates were collected from burn wound infections of hospitalised patients. Antimicrobial susceptibility of the isolates was determined, and genotyping analysis was performed by repetitive extragenic palindromic PCR (rep-PCR). PCR assay was performed to investigate the distribution of β-lactamase, aminoglycoside-modifying enzyme and efflux pump genes., Results: Etest results revealed that the most active antimicrobial agent was colistin (100% susceptibility), followed by tigecycline (96.3%). The bla OXA-51 and bla ADC genes were detected in all of the isolates, but bla OXA-58-like was not detected. The prevalence of bla TEM , bla IMP , bla VIM , bla OXA-23-like and bla OXA-24-like genes was 64.8%, 70.4%, 70.4%, 66.7% and 68.5%, respectively. ISAba1 was detected upstream of bla OXA-23-like and bla ADC in 66.7% and 77.8% of isolates, respectively. This study showed a high level of distribution of adeB (72.2%), aphA6 (81.5%), aacC1 (85.2%), aadA1 (59.3%), aadB (31.5%), tetB (70.4%) and aphA1 (29.6%) in A. baumannii strains. Based on rep-PCR analysis, four clusters (I-IV) were defined., Conclusions: The elevated prevalence of MDR A. baumannii strains in this burn centre suggests that local antibiotic prescription policies should be precisely revised. Moreover, strict infection control procedures to prevent further dissemination need to be prioritised immediately., (Copyright © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

This study determined the mechanisms and patterns of antimicrobial resistance among the isolates obtained from different wards of a teaching hospital in the city of Mashhad in north-east Iran. Between January 2012 and the end of June 2012, 36 isolates of Acinetobacter baumannii were collected from different wards of Ghaem Hospital. Antimicrobial susceptibility testing and epsilometer testing (E-test) were performed. The genetic resistance determinants of A, B and D classes of β-lactamases, aminoglycoside modifying enzymes (AMEs), efflux pumps and ISAba1 elements were assessed by PCR. Repetitive extragenic palindromic element (REP)-PCR was performed to find the genetic relatedness of the isolates. Colistin was the most effective antibiotic of those tested, where all isolates were susceptible. E-test results revealed high rates of resistance to imipenem, ceftazidime and ciprofloxacin. The majority of isolates (97  %) were multidrug-resistant. OXA-51, OXA-23 and tetB genes were detected in all isolates, but OXA-58, IMP and tetA were not detected. The prevalence of OXA-24, bla(TEM), bla(ADC), bla(VIM) and adeB were 64, 95, 61, 64 and 86  %, respectively. ISAba1 was found to be inserted into the 5' end of OXA-23 in 35 isolates (97  %). Of the AMEs, aadA1 (89  %) was the most prevalent, followed by aphA1 (75  %). The band patterns reproduced by REP-PCR showed that 34 out of 36 isolates belonged to one clone and two singletons were identified. The results confirmed that refractory A. baumannii isolates were widely distributed and warned the hospital infection control team to exert strict measures to control the infection. An urgent surveillance system should be implemented.