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Title: Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit

Abstract

Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early infection affect viral fitness has not been well studied. We generated paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection from 10 infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo viruses to their cognate T/F viruses. We found that all ten 6-mo viruses were less fit than their cognate T/F viruses. Moreover, the fitness losses of the 6-mo viruses correlated with the decrease in viral loads from the peak of viremia. Furthermore, these results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.

Authors:
 [1];  [2];  [1];  [3];  [3];  [4];  [4];  [4];  [5];  [5]; ORCiD logo [6]; ORCiD logo [6];  [1]
  1. Jilin Univ., Jilin Province (China); Duke Univ. Medical Center, Durham, NC (United States)
  2. Jilin Univ., Jilin Province (China); Duke Univ. Medical Center, Durham, NC (United States); National Inst. for Food and Drug Control, Beijing (China)
  3. Duke Univ. Medical Center, Durham, NC (United States)
  4. Univ. of Alabama at Birmingham, Birmingham, AL (United States)
  5. Jilin Univ., Jilin Province (China)
  6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1579704
Report Number(s):
LA-UR-19-30331
Journal ID: ISSN 0163-4453
Grant/Contract Number:  
89233218CNA000001; R01AI087520; R01AI028433; R01OD011095; AI067854; AI100645; 31670162; 2018ZX10731101-001-010; 2017TD-05; BX20180124; 2018M641786
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Infection
Additional Journal Information:
Journal Volume: 80; Journal Issue: 2; Journal ID: ISSN 0163-4453
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; HIV-1; Mutation; Fitness; Transmitted/founder virus; Infection

Citation Formats

Wang, Chu, Liu, Donglai, Zuo, Tao, Hora, Bhavna, Cai, Fangping, Ding, Haitao, Kappes, John, Ochsenbauer, Christina, Kong, Wei, Yu, Xianghui, Bhattacharya, Tanmoy, Perelson, Alan S., and Gao, Feng. Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit. United States: N. p., 2019. Web. doi:10.1016/j.jinf.2019.12.001.
Wang, Chu, Liu, Donglai, Zuo, Tao, Hora, Bhavna, Cai, Fangping, Ding, Haitao, Kappes, John, Ochsenbauer, Christina, Kong, Wei, Yu, Xianghui, Bhattacharya, Tanmoy, Perelson, Alan S., & Gao, Feng. Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit. United States. doi:10.1016/j.jinf.2019.12.001.
Wang, Chu, Liu, Donglai, Zuo, Tao, Hora, Bhavna, Cai, Fangping, Ding, Haitao, Kappes, John, Ochsenbauer, Christina, Kong, Wei, Yu, Xianghui, Bhattacharya, Tanmoy, Perelson, Alan S., and Gao, Feng. Thu . "Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit". United States. doi:10.1016/j.jinf.2019.12.001. https://www.osti.gov/servlets/purl/1579704.
@article{osti_1579704,
title = {Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit},
author = {Wang, Chu and Liu, Donglai and Zuo, Tao and Hora, Bhavna and Cai, Fangping and Ding, Haitao and Kappes, John and Ochsenbauer, Christina and Kong, Wei and Yu, Xianghui and Bhattacharya, Tanmoy and Perelson, Alan S. and Gao, Feng},
abstractNote = {Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early infection affect viral fitness has not been well studied. We generated paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection from 10 infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo viruses to their cognate T/F viruses. We found that all ten 6-mo viruses were less fit than their cognate T/F viruses. Moreover, the fitness losses of the 6-mo viruses correlated with the decrease in viral loads from the peak of viremia. Furthermore, these results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.},
doi = {10.1016/j.jinf.2019.12.001},
journal = {Journal of Infection},
number = 2,
volume = 80,
place = {United States},
year = {2019},
month = {12}
}

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