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HIV-1 escapes by acquiring mutations that differentially influence the course of infection. Unlike HIV-1 structural and enzymatic proteins, it remains elusive what extent the host immune-mediated selection pressure influences the variability of the accessory (Vif, Vpu, Vpr, and Nef) and regulatory (Tat and Rev) proteins. To address this, we analyzed the viral sequences encoding accessory and regulatory proteins from 446 human leukocyte antigen (HLA)-typed, chronically HIV-1 subtype B-infected, and treatment-naive individuals in Japan. We observed that Vpu and Vpr were the most and least polymorphic proteins with the average Shannon entropy scores of 0.63 and 0.38, respectively. Phylogenetically corrected methods identified a total of 161 HLA-associated polymorphisms; whereby Nef and Vpu had the highest (26.6%) and lowest (1.2%) proportion of amino acid sites associated with HLA-class I alleles, respectively. These results add further insight on the role of HLA-mediated selection pressure on HIV-1 sequence polymorphisms of HIV-1 accessory and regulatory proteins.

Aim: This study for the first time in Mwanza, Tanzania aimed at determining seropositivity of mumps virus in school aged children who are targeted for vaccination. Study Design: Cross-sectional study. Place and Duration of the Study: This study was conducted in the city of Mwanza from July to September 2018. Despite being common with reported associated complications in many resource limited countries, there is scarcity of information on its epidemiology in Tanzania. Methodology: We enrolled 440 school children aged 6-12 years. Data was collected using a pre-tested structured data collection tool. Blood samples were collected, and sera were used for detection of mumps virus antibodies by indirect enzyme linked immunosorbent assay (ELISA). Data was analyzed using STATA version 13, 2013. Results: The median age of enrolled children was 9(IQR: 8-11) years. The seropositivity of mumps IgG antibodies was found to be 94(21.4%, 95% CI: 17.5-25.1) while that of IgM was 1 (0.23%, 95% CI: 0.02-0.6). By multivariable logistic regression analysis, residing in rural areas (OR: 2.28, 95% 1.42-3.36, P=0.001) and age >10 years (OR: 1.67, 95% CI: 1.03-2.7, P=0.036) independently predicted mumps IgG seropositivity. Conclusion: A significant proportion of young children in urban areas of the city of Mwanza are susceptible to mumps virus infection indicating the need to generate more data across the country so as to institute appropriate control measures including measles, mumps and rubella (MMR) vaccination programme.

Tanzania has recently adapted World Health Organization antiretroviral guidelines that include integrase strand transfer inhibitors (INSTIs) in the first-line regimen. However, there is lack of evidence on integrase (IN) gene polymorphisms in viral strains circulating in Tanzania. In this study, we characterize IN gene polymorphisms in viral strains circulating in Dar es Salaam, Tanzania, before introduction of INSTIs. Plasma viral RNAs were prepared from 158 HIV-1-infected subjects, including 111 treated, but viremic (INSTI-naive), subjects. A part of the pol gene encompassing the IN-coding region was amplified and directly sequenced by the Sanger sequencing method. Subtype analysis revealed that subtypes A1, C, and D and intersubtype recombinants were 42%, 38%, 11%, and 9%, respectively. Although multiple subtypes cocirculate, the IN gene exhibited a relatively conserved amino acid sequence pattern with an average Shannon entropy score of 0.16. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects.

HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.

HIV-1 Nef plays an essential role in enhancing virion infectivity by antagonizing the host restriction molecule SERINC5. Because Nef is highly polymorphic due to the selective forces of host cellular immunity, we hypothesized that certain immune-escape polymorphisms may impair Nef’s ability to antagonize SERINC5 and thereby influence viral fitness in vivo. To test this hypothesis, we identified 58 Nef polymorphisms that were overrepresented in HIV-infected patients in Japan sharing the same HLA genotypes. The number of immune-associated Nef polymorphisms was inversely correlated with the plasma viral load. By breaking down the specific HLA allele-associated mutations, we found that a number of the HLA-B*51:01-associated Y120F and Q125H mutations were most significantly associated with a reduced plasma viral load. A series of biochemical experiments showed that the double mutations Y120F/Q125H, but not either single mutation, impaired Nef’s ability to antagonize SERINC5 and was associated with decreasing virion infectivity and viral replication in primary lymphocytes. In contrast, other Nef functions such as CD4, CCR5, CXCR4 and HLA class I downregulation and CD74 upregulation remained unchanged. Taken together, our results suggest that the differential ability of Nef to counteract SERINC5 by naturally occurring immune-associated mutations was associated with the plasma viral load in vivo.

Background Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. Methods This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 μg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. Results Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07–69.88, p = 0.01). Conclusions High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.

HIV-1 viral protein R (Vpr) plays important roles in HIV-1 replication. Despite the identification of a number of HLA class I-associated immune escape mutations; it is yet known whether immune-driven Vpr polymorphisms are associated with disease outcome. Hereby, we comprehensively analyzed Vpr sequence polymorphisms and their association with disease outcome and host HLA genotypes, by using plasma viral RNA isolated from 444 HLA-typed, treatment-naive, chronically HIV-1 infected individuals. Vpr amino acid residues at positions 13, 37, 45, 55, 63, 77, 84, 85, 86, and 93 were significantly associated with patients' plasma viral load and/or CD4 count. Further analysis revealed Ala at position 55 was significantly associated with lower plasma viral load; and Thr at position 63 was significantly associated with lower plasma viral load and higher CD4 count. Also, the number of amino acid residues at the two positions, located in a functionally important α-helical domain, correlated inversely with plasma viral load and positively with CD4 count. Moreover, a phylogenetically corrected method revealed residues at positions 55 and 63 are associated with patients' HLA genotypes. Taken together, our results suggest that Vpr polymorphisms at functionally important and immune-reactive sites may contribute, at least in part, to viral replication and disease outcome in vivo. J. Med. Virol. 89:123-129, 2017. © 2016 Wiley Periodicals, Inc.

Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4+ T lymphocyte subset has provided a great setback towards viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency.