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Volume 6 Supplement 3

AIDS Vaccine 2009

  • Poster presentation
  • Open Access

P20-19 LB. Extensive HLA-driven viral diversity following a single-source HIV-1 outbreak in rural China

  • T Dong1,
  • Y Zhang1,
  • K Xu1,
  • H Yan1,
  • I James1,
  • Y Peng1,
  • M blais1,
  • S Gaudieri1,
  • X Chen1,
  • W Lun1,
  • H Wu1,
  • W Qu1,
  • C Zhao1,
  • N Li1,
  • Y Mao1,
  • T Rostron1,
  • S Mallal1,
  • X Xu1,
  • A McMichael1,
  • M John1 and
  • S Rowland-Jones1
Retrovirology20096(Suppl 3):P423

https://doi.org/10.1186/1742-4690-6-S3-P423

Published: 22 October 2009

Keywords

ELISPOT AssayViral DiversityViral ControlSequence ClusterPlasma Donor

Background

High rates of mutation in HIV infected individual allow the virus to adapt rapidly in vivo to selective forces such as anti-retroviral therapy (ART) and host immune pressure. This provides an opportunity to determine the relative contribution of different components of the immune response to HIV-1 infection in driving viral diversity, which may also facilitate assessment of their role in controlling viral replication. It is accepted that HIV-1-specific cytotoxic T-lymphocytes (CTL) may drive the selection of viral variants that can escape T-cell recognition but the extent of this selective pressure has been controversial.

Methods

Two digit HLA typing; ELISPOT assay; HIV-1 sequence analysis; HIV sequence clustering and phylogenetic analysis of HLA associations using the neighbour-joining method, S-Plus 8.0, ''Partitioning around medoids'' (PAM) method and Stratification analysis by Mantel-Haenszel tests.

Results

Here we describe the consequences of HLA-associated selection on viral diversity in the main targets of T-cell recognition following an outbreak of HIV-1 in a cohort of 258 former plasma donors in rural China. The surprising finding that all the donors appear to have been infected with the same strain of clade B HIV-1 ensured that the analysis was not confounded by ''founder effect''. At least 32.63% (232/711) of the mutations in the gag, pol and nef genes leading to amino acid substitutions were associated with class I HLA molecules: of these, 27.16% (63/232) were found within or close to known CD8+ T-cell epitopes.

Conclusion

Taken together our data confirm that CD8+ T-cell pressure has a major impact on HIV-1 viral diversity and represent an important element of viral control in the infected host.

Authors’ Affiliations

(1)
Medical Research Councile, UK, Oxford, UK

Copyright

© Dong et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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