Extensive HLA-driven viral diversity following a single-source HIV-1 outbreak in rural China
Dong, T., Zhang, Y., Xu, K., Yan, H., James, I., Peng, Y., Blais, M., Gaudieri, S., Chen, X., Lun, W., Wu, H., Qu, W., Zhoo, C., Li, N., Mao, Y., Rostron, T., Mallal, S., Xu, X., McMichael, A., John, M. and Rowland-Jones, S. (2009) Extensive HLA-driven viral diversity following a single-source HIV-1 outbreak in rural China. In: AIDS Vaccine 2009, 19 - 22 October 2009, Paris, France.
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.
|Publication Type:||Conference Item|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
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