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

Retrovirology

Bhavna Hora¹  Nilu Goonetilleke²  Mark Berrong³  Guido Ferrari³  Donglai Liu⁴  Tao Zuo⁴  Chu Wang⁴  Feng Gao⁴  Alan S. Perelson⁵  Tanmoy Bhattacharya⁵  Andrew J. McMichael⁶  Michael K. P. Liu⁶ 

[1] Department of Medicine, Duke Human Vaccine Institute, Duke University Medical Center;Department of Microbiology, Immunology and Medicine, University of North Carolina at Chapel Hill;Department of Surgery, Duke University Medical Center;National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University;Theoretical Division, Los Alamos National Laboratory;Weatherall Institute of Molecular Medicine, University of Oxford;

关键词: Mutation;    Selection;    Immune responses;    Cryptic T cell response;    Fitness;    Escape;   

DOI  :  10.1186/s12977-017-0371-4

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown