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Journal of Virology, October 2004, p. 11208-11218, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11208-11218.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Multiple V1/V2 env Variants Are Frequently Present during Primary Infection with Human Immunodeficiency Virus Type 1

Kimberly Ritola,1,2 Christopher D. Pilcher,1,3 Susan A. Fiscus,1,4 Noah G. Hoffman,1,4 Julie A. E. Nelson,1 Kathryn M. Kitrinos,1,2,{ddagger} Charles B. Hicks,5 Joseph J. Eron Jr.,1,3 and Ronald Swanstrom1,4,6*

UNC Center for AIDS Research,1 Curriculum in Genetics and Molecular Biology,2 Departments of Medicine,3 Microbiology and Immunology,4 Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill,6 Department of Medicine, Duke University, Durham, North Carolina5

Received 13 October 2003/ Accepted 15 July 2004

Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is a low-probability event in which there is thought to be low genetic complexity in the initial inoculum. In order to assess the viral complexity present during primary HIV-1 infection, the V1/V2 and V3 variable regions of the env gene were examined by using a heteroduplex tracking assay (HTA) capable of resolving these genotypic variants. Blood plasma samples from 26 primary HIV-1-infected subjects were analyzed for their level of diversity. Half of the subjects had more than one V1/V2 viral variant during primary infection, indicating the frequent transmission of multiple variants. This observation is inconsistent with the idea of infrequent transmission based on a small transmitting inoculum of cell-free virus. In chronically infected subjects, the complexity of the viral populations was even greater in both the V1/V2 and the V3 regions than in acutely infected subjects, indicating that in spite of the presence of multiple variants in acute infection, the virus does pass through a genetic bottleneck during transmission. We also examined how well the infecting virus penetrated different anatomical compartments by using the HTA. Viral variants detected in blood plasma were compared to those detected in seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each of these compartments was to a large extent identical to virus in blood plasma, a finding consistent with rapid penetration of the infecting variant(s). The low-probability transmission of multiple variants could be the result of transient periods of hyperinfectiousness or hypersusceptibility. Alternatively, the inefficient transfer of a multiply infected cell could account for both the low probability of transmission and the transfer of multiple variants.

* Corresponding author. Mailing address: University of North Carolina at Chapel Hill, 22-062 Lineberger Cancer Center, CB 7295, Chapel Hill, NC 27599-7295. Phone: (919) 966-5710. Fax: (919) 966-8212. E-mail: risunc{at}med.unc.edu.

{ddagger} Present address: Department of Clinical Virology, GlaxoSmithKline, Durham, NC 27709-3398.

Journal of Virology, October 2004, p. 11208-11218, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11208-11218.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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