Conserved positive selection signals in HIV-1 gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection.
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Date
2008
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central.
Abstract
Background.
The high diversity of HIV variants driving the global AIDS epidemic has caused
many to doubt whether an effective vaccine against the virus is possible. However,
by identifying the selective forces that are driving the ongoing diversification of HIV
and characterising their genetic consequences, it may be possible to design vaccines
that pre-empt some of the virus’ more common evasion tactics. One component of
such vaccines might be the envelope protein, gp41. Besides being targeted by both
the humoral and cellular arms of the immune system this protein mediates fusion
between viral and target cell membranes and is likely to be a primary determinant of
HIV transmissibility. Results. Using recombination aware analysis tools we compared site specific signals of
selection in gp41 sequences from different HIV-1 M subtypes and circulating
recombinant forms and identified twelve sites evolving under positive selection across
multiple major HIV-1 lineages. To identify evidence of selection operating during
transmission our analysis included two matched datasets sampled from patients with
acute or chronic subtype C infections. We identified six gp41 sites apparently
evolving under different selection pressures during acute and chronic HIV-1
infections. These sites mostly fell within functional gp41 domains, with one site
located within the epitope recognised by the broadly neutralizing antibody, 4E10.
Conclusions. Whereas these six sites are potentially determinants of fitness and are therefore good
candidate targets for subtype-C specific vaccines, the twelve sites evolving under diversifying selection across multiple subtypes might make good candidate targets for broadly protective vaccines.
Description
Keywords
HIV infections--Virology., AIDS (Disease)--Vaccines., AIDS (Disease)--Virology.
Citation
Bandawe, G.P., et al. 2008.Conserved positive selection signals in HIV-1 gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection. Virology Journal 5:141 doi:10.1186/1743-422X-5-141