P09-11. Reduced Replication Capacity of NL4-3 Chimeric Viruses Encoding RT-Integrase Sequences from HIV-1 Elite Controllers

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P09-11. Reduced Replication Capacity of NL4-3 Chimeric Viruses Encoding RT-Integrase Sequences from HIV-1 Elite Controllers

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dc.contributor.author Brumme, ZL
dc.contributor.author Miura, T
dc.contributor.author Rosato, PC
dc.contributor.author Sela, J
dc.contributor.author Brumme, CJ
dc.contributor.author Heckerman, D
dc.contributor.author Walker, BD
dc.contributor.author Brockman, Mark
dc.contributor.author Pereyra, Florencia M.
dc.contributor.author Li, C
dc.date.accessioned 2012-02-05T22:07:24Z
dc.date.issued 2009
dc.identifier.citation Li, C, ZL Brumme, T Miura, PC Rosato, J Sela, CJ Brumme, D Heckerman, F Pereyra, BD Walker, and MA Brockman. 2009. P09-11. Reduced replication capacity of NL4-3 chimeric viruses encoding RT-Integrase sequences from HIV-1 elite controllers. Retrovirology 6(Suppl 3): P124. en_US
dc.identifier.issn 1742-4690 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8123174
dc.description.abstract Background: Spontaneous control of HIV to <50 copies RNA/ml is observed in rare individuals. An improved understanding of this phenomenon may provide insight into host mechanisms that can be modulated for therapeutic benefit by vaccines. Recent studies of these 'elite' controllers (EC) revealed HLA-associated changes in Gag-Protease that resulted in reduced replication capacity. This project assessed the possibility of immune-mediated defects in the Pol gene (RT-Integrase) of EC. Methods: Chimeric NL4-3 mutants encoding patient plasmaderived RT-Integrase sequences from EC (N = 58) and chronic progressors (N = 50) were constructed by homologous recombination. Replication capacity (RC) for each variant strain was assessed using a GFP-reporter T cell assay. Results were correlated with clinical and host genetic factors, including CD4 count, plasma viral load (pVL), and patient HLA. Results: Viruses encoding Pol sequences from EC replicated significantly less well than those from individuals with progressive disease (Mann-Whitney, p < 0.0001). No association was observed between RC and CD4 T cell count in EC or progressors, nor between RC and pVL in progressors (Spearman, all p > 0.05). Viruses derived from HLA-B57+ EC (N = 20) appeared to replicate slower than those from B57+ progressors (N = 8) (p = 0.004). Similar results were observed between B51+ EC (N = 4) and B51+ progressors (N = 10) (p = 0.024), but not between B27+ EC (N = 9) and B27+ progressors (N = 5) (p = 0.437). Conclusion: This study extends previous observations for Gag and demonstrates that Pol variants from EC also display reduced function. The association between fitness and expression of certain HLA that present Pol epitopes suggests that immune-mediated mutations impairing viral fitness may play a key role in spontaneous control of HIV. Results indicate that HLA alleles responsible for such defects in protein function may differ among viral genes. Further identification of HLA-associated changes in HIV may allow design of vaccines targeting the most vulnerable regions of the virus. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi://10.1186/1742-4690-6-S3-P124 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767609/pdf/ en_US
dash.license LAA
dc.title P09-11. Reduced Replication Capacity of NL4-3 Chimeric Viruses Encoding RT-Integrase Sequences from HIV-1 Elite Controllers en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Retrovirology en_US
dash.depositing.author Pereyra, Florencia M.
dc.date.available 2012-02-05T22:07:24Z
dash.affiliation.other SPH^Biostatistics en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US

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