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

Journal Article · · Retrovirology
 [1];  [1];  [2];  [1];  [3];  [4];  [5];  [5];  [4];  [6];  [6]; ORCiD logo [1]
  1. Jilin Univ., Changchun (China). National Engineering Lab. for AIDS Vaccine, School of Life Sciences; Duke Univ., Durham, NC (United States). Medical Center, Duke Human Vaccine Inst., Dept. of Medicine
  2. Duke Univ., Durham, NC (United States). Medical Center, Duke Human Vaccine Inst., Dept. of Medicine
  3. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Microbiology, Immunology and Medicine
  4. Univ. of Oxford (United Kingdom). Weatherall Inst. of Molecular Medicine
  5. Duke Univ., Durham, NC (United States). Medical Center, Dept. of Surgery
  6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division
+ Show Author Affiliations

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. 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. In conclusion, 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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Natural Science Foundation of China (NSFC); USDOE
Grant/Contract Number:
AC52-06NA25396; 31670162; AI067854; AI100645; AI028433; OD011095
OSTI ID:
1418764
Report Number(s):
LA-UR-17-21998
Journal Information:
Retrovirology, Vol. 14, Issue 1; ISSN 1742-4690
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 2 works
Citation information provided by
Web of Science

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59 BASIC BIOLOGICAL SCIENCES
Biological Science
Mutation
Selection
Immune responses
Cryptic T cell response
Fitness
Escape