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Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate.

ABSTRACT: Although stretches of serine and threonine are sometimes sites for O-linked carbohydrate attachment, specific sequence and structural determinants for O-linked attachment remain ill defined. The gp120 envelope protein of SIVmac239 contains a serine-threonine-rich stretch of amino acids at positions 128 to 139. Here we show that lectin protein from jackfruit seed (jacalin), which binds to non- and monosialylated core 1 O-linked carbohydrate, potently inhibited the replication of SIVmac239. Selection of a jacalin-resistant SIVmac239 variant population resulted in virus with specific substitutions within amino acids 128 to 139. Cloned simian immunodeficiency virus (SIV) variants with substitutions in the 128-to-139 region had infectivities equivalent to, or within 1 log unit of, that of SIVmac239 and were resistant to the inhibitory effects of jacalin. Characterization of the SIVmac239 gp120 O-linked glycome showed the presence of core 1 and core 2 O-linked carbohydrate; a 128-to-139-substituted variant gp120 from jacalin-resistant SIV lacked O-linked carbohydrate. Unlike that of SIVmac239, the replication of HIV-1 strain NL4-3 was resistant to inhibition by jacalin. Purified gp120s from four SIVmac and SIVsm strains bound jacalin strongly in an enzyme-linked immunosorbent assay, while nine different HIV-1 gp120s, two SIVcpz gp120s, and 128-to-139-substituted SIVmac239 gp120 did not bind jacalin. The ability or inability to bind jacalin thus correlated with the presence of the serine-threonine-rich stretch in the SIVmac and SIVsm gp120s and the absence of such stretches in the SIVcpz and HIV-1 gp120s. Consistent with sequence predictions, two HIV-2 gp120s bound jacalin, while one did not. These data demonstrate the presence of non- and monosialylated core 1 O-linked carbohydrate on the gp120s of SIVmac and SIVsm and the lack of these modifications on HIV-1 and SIVcpz gp120s.

SUBMITTER: Stansell E

PROVIDER: S-EPMC3014205 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate.

Stansell Elizabeth E Canis Kevin K Haslam Stuart M SM Dell Anne A Desrosiers Ronald C RC

Journal of virology 20101020 1

Although stretches of serine and threonine are sometimes sites for O-linked carbohydrate attachment, specific sequence and structural determinants for O-linked attachment remain ill defined. The gp120 envelope protein of SIVmac239 contains a serine-threonine-rich stretch of amino acids at positions 128 to 139. Here we show that lectin protein from jackfruit seed (jacalin), which binds to non- and monosialylated core 1 O-linked carbohydrate, potently inhibited the replication of SIVmac239. Select ...[more]

PMID: 20962077

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Project description:To explore the differences between the extreme SIV infection phenotypes, nonprogression (BEN: benign) to AIDS in sooty mangabeys (SMs) and progression to AIDS (MAL: malignant) in rhesus macaques (RMs), we performed an integrated dual positive-negative connectivity (DPNC) analysis of gene coexpression networks (GCN) based on publicly available big data sets in the GEO database of NCBI. The microarray-based gene expression data sets were generated, respectively, from the peripheral blood of SMs and RMs at several time points of SIV infection. Significant differences of GCN changes in DPNC values were observed in SIV-infected SMs and RMs. There are three groups of enriched genes or pathways (EGPs) that are associated with three SIV infection phenotypes (BEN+, MAL+ and mixed BEN+/MAL+). The MAL+ phenotype in SIV-infected RMs is specifically associated with eight EGPs, including the protein ubiquitin proteasome system, p53, granzyme A, gramzyme B, polo-like kinase, Glucocorticoid receptor, oxidative phosyphorylation and mitochondrial signaling. Mitochondrial (endosymbiotic) dysfunction is solely present in RMs. Specific BEN+ pattern changes in four EGPs are identified in SIV-infected SMs, including the pathways contributing to interferon signaling, BRCA1/DNA damage response, PKR/INF induction and LGALS8. There are three enriched pathways (PRR-activated IRF signaling, RIG1-like receptor and PRR pathway) contributing to the mixed (BEN+/MAL+) phenotypes of SIV infections in RMs and SMs, suggesting that these pathways play a dual role in the host defense against viral infections. Further analysis of Hub genes in these GCNs revealed that the genes LGALS8 and IL-17RA, which positively regulate the barrier function of the gut mucosa and the immune homeostasis with the gut microbiota (exosymbiosis), were significantly differentially expressed in RMs and SMs. Our data suggest that there exists an exo- (dysbiosis of the gut microbiota) and endo- (mitochondrial dysfunction) symbiotic imbalance (EESI) in HIV/SIV infections. Dissecting the mechanisms of the exo-endo symbiotic balance (EESB) that maintains immune homeostasis and the EESI problems in HIV/SIV infections may lead to a better understanding of the pathogenesis of AIDS and the development of novel interventions for the rational control of this disease.

Dataset Information

Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate.

Publications

Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate.

Similar Datasets

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