Conserved positive selection signals in gp41 across multiple subtypes and difference in selection signals detectable in gp41 sequences sampled during acute and chronic HIV-1 subtype C infection.
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.
Bandawe
Gama P
GP
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa. gama.bandawe@uct.ac.za
Martin
Darren P
DP
Treurnicht
Florette
F
Mlisana
Koleka
K
Karim
Salim S Abdool
SS
Williamson
Carolyn
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D019943:Amino Acid Substitution; D003062:Codon; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D020125:Mutation, Missense; D017354:Point Mutation; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
D003062:Codon; D018985:Epitopes, B-Lymphocyte; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1