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HLA‐A, ‐C, ‐B, and ‐DRB1 genotypes were analyzed in 178 Japanese COVID‐19 patients to investigate the association of HLA with severe COVID‐19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA‐DRB1*09:01 and severe COVID‐19 (odds ratio [OR], 3.62; 95% CI, 1.57–8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID‐19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID‐19. [ABSTRACT FROM AUTHOR]

Abstract: Global antibody glycosylation is dynamic and plays critical roles in shaping different immunological outcomes and direct antibody functionality during HIV infection. However, the relevance of global antibody or plasma glycosylation patterns to HIV persistence after antiretroviral therapy (ART) has not been characterized. First, we compared glycomes of total plasma and isolated immunoglobulin G (IgG) from HIV+ ART‐suppressed, HIV+ viremic, and HIV‐negative individuals. Second, in ART‐suppressed individuals, we examined the associations between glycomes and (1) levels of cell‐associated HIV DNA and RNA in PBMCs and isolated CD4+ T cells, (2) CD4 count and CD4%, and (3) expression of CD4+ T‐cell activation markers. HIV infection is associated with persistent alterations in the IgG glycome including decreased levels of disialylated glycans, which is associated with a lower anti‐inflammatory activity, and increased levels of fucosylated glycans, which is associated with lower antibody‐dependent cell‐mediated cytotoxicity (ADCC). We also show that levels of certain mono‐ and digalactosylated nonfucosylated glycomic traits (A2G1, A2G2, and A2BG2), which have been reported to be associated with higher ADCC and higher anti‐inflammatory activities, exhibit significant negative correlations with levels of cell‐associated total HIV DNA and HIV RNA in ART‐suppressed individuals. Finally, levels of certain circulating anti‐inflammatory glycans are associated with higher levels of CD4 T cells and lower levels of T‐cell activation. Our findings represent the first proof‐of‐concept evidence that glycomic alterations, known to be associated with differential states of inflammation and ADCC activities, are also associated with levels of HIV persistence in the setting of ART suppression. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance. [ABSTRACT FROM AUTHOR]