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Accumulated Mutations Cause Significant Fitness Losses and are Associated with Decreased Viral Loads During Early HIV-1 Infection

57 Pages Posted: 23 Jan 2019 Sneak Peek Status: Review Complete

See all articles by Chu Wang

Chu Wang

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine; Duke University - Department of Medicine

Donglai Liu

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine; Duke University - Department of Medicine; Government of the People's Republic of China - Division of the Second in Vitro Diagnostic

Tao Zuo

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine; Duke University - Department of Medicine

Bhavna Hora

Duke University - Department of Medicine

Fangping Cai

Duke University - Department of Medicine

Haitao Ding

University of Alabama at Birmingham - Department of Medicine

John Kappes

University of Alabama at Birmingham - Department of Medicine

Christina Ochsenbauer

University of Alabama at Birmingham - Department of Medicine

Wei Kong

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Xianghui Yu

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Tanmoy Bhattacharya

Government of the United States of America - Theoretical Division

Alan S. Perelson

Government of the United States of America - Theoretical Division

Feng Gao

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine; Duke University - Department of Medicine

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Abstract

Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early and chronic infection affect viral fitness has not been well studied. We generated infectious molecular clones (IMCs) for the transmitted/founder (T/F), 6-month (6-mo) and 2-year (2-yr) viruses from the same infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo or 2-yr viruses to their cognate T/F viruses. We found that all ten 6-mo viruses were less fit than their cognate T/F viruses. Interestingly, 2-yr viruses that represented the clonally expanded viruses were more fit than the T/F viruses in two individuals. The fitness losses of the 6-mo viruses correlated with the decrease in viral loads from peak viremia. These results show that the mutations at month 6 of infection significantly reduce viral fitness and thereby contribute to lowering viral loads.

Suggested Citation

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, Accumulated Mutations Cause Significant Fitness Losses and are Associated with Decreased Viral Loads During Early HIV-1 Infection (January 19, 2019). Available at SSRN: https://ssrn.com/abstract=3318932 or http://dx.doi.org/10.2139/ssrn.3318932
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Chu Wang

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Changchun, 130012
China

Duke University - Department of Medicine

Durham, NC 27710
United States

Donglai Liu

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Changchun, 130012
China

Duke University - Department of Medicine

Durham, NC 27710
United States

Government of the People's Republic of China - Division of the Second in Vitro Diagnostic

Beijing, 100050
China

Tao Zuo

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Changchun, 130012
China

Duke University - Department of Medicine

Durham, NC 27710
United States

Bhavna Hora

Duke University - Department of Medicine

Durham, NC 27710
United States

Fangping Cai

Duke University - Department of Medicine

Durham, NC 27710
United States

Haitao Ding

University of Alabama at Birmingham - Department of Medicine

Birmingham, AL 35294
United States

John Kappes

University of Alabama at Birmingham - Department of Medicine

Birmingham, AL 35294
United States

Christina Ochsenbauer

University of Alabama at Birmingham - Department of Medicine

Birmingham, AL 35294
United States

Wei Kong

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Changchun, 130012
China

Xianghui Yu

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine

Changchun, 130012
China

Tanmoy Bhattacharya

Government of the United States of America - Theoretical Division

Los Alamos, NM 87545
United States

Alan S. Perelson

Government of the United States of America - Theoretical Division

Los Alamos, NM 87545
United States

Feng Gao (Contact Author)

Jilin University (JLU) - National Engineering Laboratory for AIDS Vaccine ( email )

Changchun, 130012
China

Duke University - Department of Medicine ( email )

Durham, NC 27710
United States

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