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h resistance to fluconazole and voriconazole of two C. auris strains from different genetic clades, thereby providing insight into the molecular basis of drug resistance of this medically important yeast. Copyright © 2020 Mayr et al.xCT forms part of the xc – cysteine-glutamate antiporter which inhibits antimicrobial inflammatory immune functions and thus increases susceptibility to tuberculosis (TB). GA-017 nmr However, the associations between xCT gene polymorphisms and susceptibility to TB, as well as whether these modulate xCT expression or affect treatment with the xCT inhibitor sulfasalazine (SASP), are unclear. In the present study, we genotyped xCT polymorphisms in a large Chinese cohort and found that the single-nucleotide polymorphism (SNP) rs13120371 was associated with susceptibility to TB. The rs13120371 AA genotype was strongly associated with an increased risk of TB and increased xCT mRNA expression levels compared to those with the GG or AG genotype. rs13120371 is located on the 3′ untranslated (UTR) region of the xCT gene, in the putative binding site for miR-142-3p, and the results of luciferase reporter assays indicated that the rs13120371 AA genotype inhibited the binding of miR-42-3p to xCT. Bacterial burden was also significan xCT genotype can improve TB outcomes. Copyright © 2020 Wang et al.HLA-B*5201 is strongly associated with protection against HIV disease progression. However, the mechanisms of HLA-B*5201-mediated immune control have not been well-studied. We here describe a cohort with a majority of HIV C-clade infected individuals from Delhi, India where HLA-B*5201 is highly prevalent (phenotypic frequency 22.5%). Consistent with studies of other cohorts, expression of HLA-B*5201 was associated with high absolute CD4 counts and therefore a lack of HIV disease progression. We here examined the impact of HLA-B*5201-associated viral polymorphisms within the immunodominant C-clade Gag epitope RMTSPVSI (‘RI8’; Gag residues 275-282) on viral replicative capacity (VRC), since HLA-mediated reduction in VRC is a central mechanism implicated in HLA-associated control of HIV. We observed in HLA-B*5201 positive individuals a higher frequency of V280T, V280S, and V280A variants within RI8 (p=0.0001). Each of these variants reduced viral replicative capacity in C-clade viruses, particularly the V280A va HLA-B*5201 has consistently been shown in other cohorts to be associated with protection against HIV disease progression, but studies have been limited by the low prevalence of this allele in North America and Europe. Amongst the C-clade infected individuals, we show that HLA-B*5201 is the most protective of all the HLA-B alleles expressed in the Indian cohort, being associated with the highest absolute CD4 counts. Further, we show that the mechanism by which HLA-B*5201 mediates immune protection is, at least in part, related to the inability of HIV to evade the HLA-B*5201-restricted p24 Gag-specific CD8+ T-cell response without incurring a significant loss to viral replicative capacity. Copyright © 2020 American Society for Microbiology.Gammaherpesviruses are ubiquitous pathogens that are associated with cancers, including B cell lymphomas. These viruses are unique in that they infect naïve B cells and subsequently drive a robust polyclonal germinal center response in order to amplify the latent reservoir and to establish life-long infection in memory B cells. Gammaherpesvirus-driven germinal center response in combination with robust infection of germinal center B cells is thought to precipitate lymphomagenesis. Importantly, host and viral factors that selectively affect gammaherpesvirus-driven germinal center response remain poorly understood. Global deficiency of the antiviral and tumor suppressive Interferon Regulatory Factor 1 (IRF-1) selectively promotes the murine gammaherpesvirus 68 (MHV68)-driven germinal center response and expansion of the viral latent reservoir. To determine the extent to which antiviral effects of IRF-1 are B cell-intrinsic, we generated mice with conditional deficiency of IRF-1. Surprisingly, B cell-specific IRl-established tumor suppressor, selectively attenuates MHV68-driven germinal center response, a phenotype that we originally hypothesized to occur in a B cell-intrinsic manner. In contrast, when tested, B cell-intrinsic IRF-1 expression promoted the MHV68-driven germinal center response and the establishment of chronic infection. Our study highlights the underappreciated multifaceted role of IRF-1 in MHV68 infection and pathogenesis. Copyright © 2020 American Society for Microbiology.RNA modifications play diverse roles in regulating RNA function, and viruses co-opt these pathways for their own benefit. While recent studies have highlighted the importance of N6-methyladenosine (m6A)-the most abundant mRNA modification-in regulating retrovirus replication, the identification and function of other RNA modifications in viral biology have been largely unexplored. Here, we characterize the RNA modifications present in a model retrovirus, murine leukemia virus (MLV), using mass spectrometry and sequencing. We find that 5-methylcytosine (m5C) is highly enriched in viral genomic RNA relative to uninfected cellular mRNAs, and we map at single-nucleotide resolution the m5C sites, which are located in multiple clusters throughout the MLV genome. Further, we show that the m5C reader protein ALYREF plays an important role in regulating MLV replication. Together, our results provide a complete m5C profile in a virus and its function in a eukaryotic mRNA.Importance Over 130 modifications have been identified in cellular RNAs, which play critical roles in many cellular processes, from modulating RNA stability to altering translation efficiency. One such modification, 5-methylcytosine, is relatively abundant in mammalian mRNAs, but its precise location and function are not well understood. In this study, we identify unexpectedly high levels of m5C in the murine leukemia virus RNA, precisely map its location, and show that ALYREF, a “reader” protein that specifically recognizes m5C, regulates viral production. Together, our findings provide a high-resolution atlas of m5C in murine leukemia virus and reveal a functional role of m5C in viral replication. Copyright © 2020 American Society for Microbiology.