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Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep38130· OSTI ID:1624874
 [1];  [2];  [3];  [2];  [2];  [3];  [3];  [4]
  1. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine; DOE/OSTI
  2. Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division
  4. 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
+ Show Author Affiliations
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.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1624874
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 6; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (4)

Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection journal May 2018
The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage journal August 2018
Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness journal January 2017
Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses journal February 2018

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