A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies

Background: Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral ftness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in ftness losses. Results: Strongly selected mutations were identifed by analyzing 5′-half HIV-1 genome (gag/pol) sequences from longitudinal samples of subject CH0131. The K43R mutation in the gag gene was frst detected at day 91 post screening and was fxed in the viral population at day 273 while the synonymous N323tc mutation was frst detected at day 177 and fxed at day 670. No conventional or cryptic T cell responses were detected against either mutation sites by ELISpot analysis. However, when ftness costs of both mutations were measured by introducing each mutation into their cognate transmitted/founder (T/F) viral genome, the K43R mutation caused a signifcant ftness loss while the N323tc mutation had little impact on viral ftness. Conclusions: The rapid fxation, the lack of detectable immune responses and the signifcant ftness cost of the K43R mutation suggests that it was strongly selected by host factors other than T cell responses and neutralizing antibodie