Antigenic Variation of SIV: Mutations in V4 Alter the Neutralization Profile

Kinsey, Nicole E.; Anderson, Mark G.; Unangst, Tami; Joag, Sanjay V.; Narayan, Opendra; Zink, M. Christine; Clements, Janice E.

doi:10.1006/viro.1996.0348

Cited by 47 publications

(49 citation statements)

References 4 publications

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“…The neutralizing epitope profile of SIV envelope includes the CD4 binding site and gp41 but not the V3 region. There is conflicting evidence as to whether V1, V2, and/or V4 of SIV are targets for antibody neutralization (15,18,19). The present study addresses whether vaccine-induced immune responses accelerate the generation of autologous neutralizing antibodies following SIV challenge in rhesus monkeys and how this humoral immune response can potentially shape viral sequence evolution.…”

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confidence: 94%

“…SIV and HIV-1 envelopes share approximately 40% amino acid homology (10,11) and have overlapping variable and constant regions, although the variable region 3 (V3) of HIV-1 envelope does not align with the homologous region of SIV envelope (7). Following SIV infection in rhesus monkeys, SIV envelope evolves most rapidly in variable regions 1 and 4 (V1 and V4, respectively), leading to nucleotide additions, deletions, and/or mutations that can potentially translate to changes in glycosylation (7,9,13,15,19,29,30).…”

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confidence: 99%

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Envelope Vaccination Shapes Viral Envelope Evolution following Simian Immunodeficiency Virus Infection in Rhesus Monkeys

Basavapathruni

Yeh

Coffey

et al. 2010

J Virol

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The evolution of envelope mutations by replicating primate immunodeficiency viruses allows these viruses to escape from the immune pressure mediated by neutralizing antibodies. Vaccine-induced anti-envelope antibody responses may accelerate and/or alter the specificity of the antibodies, thus shaping the evolution of envelope mutations in the replicating virus. To explore this possibility, we studied the neutralizing antibody response and the envelope sequences in rhesus monkeys vaccinated with either gag-pol-nef immunogens or gag-pol-nef immunogens in combination with env and then infected with simian immunodeficiency virus (SIV). Using a pseudovirion neutralization assay, we demonstrate that envelope vaccination primed for an accelerated neutralizing antibody response following virus challenge. To monitor viral envelope evolution in these two cohorts of monkeys, full-length envelopes from plasma virus isolated at weeks 37 and 62 postchallenge were sequenced by single genome amplification to identify sites of envelope mutations. We show that env vaccination was associated with a change in the pattern of envelope mutations. Prevalent mutations in sequences from gag-pol-nef vaccinees included deletions in both variable regions 1 and 4 (V1 and V4), whereas deletions in the env vaccinees occurred only in V1. These data show that env vaccination altered the focus of the antibodymediated selection pressure on the evolution of envelope following SIV challenge.

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confidence: 94%

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confidence: 99%

Envelope Vaccination Shapes Viral Envelope Evolution following Simian Immunodeficiency Virus Infection in Rhesus Monkeys

Basavapathruni

Yeh

Coffey

et al. 2010

J Virol

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“…Lentiviral antigenic variation is most pronounced in the viral Env proteins that serve as initial primary targets for host immune responses. Studies on the effect of Env variation on antigenic properties indicate that even minor changes in amino acid sequence can dramatically alter antibody and CTL specificities in in vitro assays and immune control of persistent infections in vivo (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Nevertheless, even apparently extensive Env variations may not necessarily cause detectable changes in immune phenotype as measured by in vitro assays alone (18).…”

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confidence: 99%

Envelope variation as a primary determinant of lentiviral vaccine efficacy

Craigo

Zhang

Barnes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Lentiviral envelope antigenic variation and associated immune evasion are believed to present major obstacles to effective vaccine development. Although this perception is widely assumed by the scientific community, there is, to date, no rigorous experimental data assessing the effect of increasing levels of lentiviral Env variation on vaccine efficacy. It is our working hypothesis that Env is, in fact, a primary determinant of vaccine effectiveness. We previously reported that a successful experimental attenuated equine infectious anemia virus vaccine, derived by mutation of the viral S2 accessory gene, provided 100% protection from disease after virulent virus challenge. Here, we sought to comprehensively test our hypothesis by challenging vaccinated animals with proviral strains of defined, increasing Env variation, using variant envelope SU genes that arose naturally during experimental infection of ponies with equine infectious anemia virus. The reference attenuated vaccine combined with these variant Env challenge strains facilitated evaluation of the protection conferred by ancestral immunogens, because the Env of the attenuated vaccine is a direct ancestor to the variant proviral strain Envs. The results demonstrated that ancestral Env proteins did not impart broad levels of protection against challenge. Furthermore, the results displayed a significant inverse linear correlation of Env divergence and protection from disease. This study demonstrates potential obstacles to the use of single isolate ancestral Env immunogens. Finally, these findings reveal that relatively minor Env variation can pose a substantial challenge to lentiviral vaccine immunity, even when attenuated vaccines are used that, to date, achieve the highest levels of vaccine protection.ancestral immunogen ͉ equine infectious anemia virus ͉ lentivirus

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“…Fab 201 competed with mouse monoclonal antibodies (KK5 and KK9) that react with a conformation-dependent epitope in the V3 to V4 region (7,21). Previous studies with these mouse monoclonal antibodies have demonstrated that they are highly sensitive to substitutions within the V4 region (25). However, the V123 chimera but not the V4 or the V45 chimera was recognized by IgG1-201, restricting the region of the epitope to the V3 to C3 region.…”

Section: Vol 74 2000mentioning

confidence: 98%

“…However, many of the neutralizing epitopes for SIV have been partially mapped by peptide scanning (20,21) and mutational analysis (3,6,7,25,44). A number of studies conducted with variants of the SIVmac lineage have shown that discrete amino acid substitutions in the envelope glycoprotein can alter the neutralization phenotype (3,25,44). Such changes include the acquisition of novel glycosylation sites as a viral mechanism for avoiding recognition by neutralizing antibody (6).…”

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confidence: 99%