Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences
Abstract
A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15. However, the efficiency for different T/F viruses from the same individual to use CCR5 was significantly variable, and the differences were even more significant for usage of coreceptors FPRL1, CCR3 and APJ. Resistance to IFN-α was also different between T/F viruses in 2 of 3 individuals. The relative fitness between T/F viruses from the same subject was highly variable (2–6%). Importantly, the levels of coreceptor usage efficiency, resistance to IFN-α and viral fitness were not associated with proportions of T/F viruses in each individual during acute infection. Our results show that the modest but significant differences in coreceptor usage efficiency, IFN-α sensitivity and viral fitness each alone may not play a critical role in HIV-1 transmission.
- Authors:
-
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine; Jilin Univ., Changchun (China). School of Life Sciences. National Engineering Lab. for AIDS Vaccine
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1624874
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Science & Technology - Other Topics
Citation Formats
Song, Hongshuo, Hora, Bhavna, Giorgi, Elena E., Kumar, Amit, Cai, Fangping, Bhattacharya, Tanmoy, Perelson, Alan S., and Gao, Feng. Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences. United States: N. p., 2016.
Web. doi:10.1038/srep38130.
Song, Hongshuo, Hora, Bhavna, Giorgi, Elena E., Kumar, Amit, Cai, Fangping, Bhattacharya, Tanmoy, Perelson, Alan S., & Gao, Feng. Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences. United States. https://doi.org/10.1038/srep38130
Song, Hongshuo, Hora, Bhavna, Giorgi, Elena E., Kumar, Amit, Cai, Fangping, Bhattacharya, Tanmoy, Perelson, Alan S., and Gao, Feng. Thu .
"Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences". United States. https://doi.org/10.1038/srep38130. https://www.osti.gov/servlets/purl/1624874.
@article{osti_1624874,
title = {Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences},
author = {Song, Hongshuo and Hora, Bhavna and Giorgi, Elena E. and Kumar, Amit and Cai, Fangping and Bhattacharya, Tanmoy and Perelson, Alan S. and Gao, Feng},
abstractNote = {A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15. However, the efficiency for different T/F viruses from the same individual to use CCR5 was significantly variable, and the differences were even more significant for usage of coreceptors FPRL1, CCR3 and APJ. Resistance to IFN-α was also different between T/F viruses in 2 of 3 individuals. The relative fitness between T/F viruses from the same subject was highly variable (2–6%). Importantly, the levels of coreceptor usage efficiency, resistance to IFN-α and viral fitness were not associated with proportions of T/F viruses in each individual during acute infection. Our results show that the modest but significant differences in coreceptor usage efficiency, IFN-α sensitivity and viral fitness each alone may not play a critical role in HIV-1 transmission.},
doi = {10.1038/srep38130},
journal = {Scientific Reports},
number = 1,
volume = 6,
place = {United States},
year = {Thu Dec 01 00:00:00 EST 2016},
month = {Thu Dec 01 00:00:00 EST 2016}
}
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Works referencing / citing this record:
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