Chu Wang1, Donglai Liu2, Tao Zuo1, Bhavna Hora3, Fangping Cai3, Haitao Ding4, John Kappes4, Christina Ochsenbauer4, Wei Kong5, Xianghui Yu5, Tanmoy Bhattacharya6, Alan S Perelson6, Feng Gao7. 1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. 2. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Division of the Second in Vitro Diagnostic, National Institute for Food and Drug Control, Beijing 100050, China. 3. Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. 4. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. 5. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China. 6. Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. 7. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin, China; Department of Medicine and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: fgao@duke.edu.
Abstract
OBJECTIVE: 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. METHODS: Paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection were generated 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. RESULTS: 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. CONCLUSION: These results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.
OBJECTIVE: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. METHODS: Paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection were generated 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. RESULTS: 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. CONCLUSION: These results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.
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