Abstract

The env gene of HIV-1 rapidly evolves. One important determinant of envevolution is selection for altered co-receptor use. Change in co-receptor use represents an important change in the biology of the virus that is correlated with accelerated disease progression. The PI has recently applied a new technology, heteroduplex tracking analysis (HTA), to study alterations in the V3 region of HIV-1 env. This region of env is the major co- receptor use determinant. The Pi proposes to use this assay to study the evolution of in V3 in patients who are at risk for the development of V3 evolutionary variants, who have undergone dramatic losses of CD4+ T- cells, and who have undergone antiretroviral therapy. They will also use this assay to study the relative growth rates of V3 variants in several model systems. They will use an experimental protocol based on strong genetic selection to explore the determinants of co-receptor use and analyze interactions with co-receptors. Finally, they will use HTA to follow specific events in other variable regions of HIV-1 env. These efforts represent a comprehensive approach to understanding the dynamic behavior of env sequence evolution and the forces driving this evolution.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044667-03
Application #
6341733
Study Section
Special Emphasis Panel (ZRG5-AARR-4 (03))
Program Officer
Sharma, Opendra K
Project Start
1999-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
3
Fiscal Year
2001
Total Cost
$266,514
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Russell, Elizabeth S; Ojeda, Suany; Fouda, Genevieve G et al. (2013) Short communication: HIV type 1 subtype C variants transmitted through the bottleneck of breastfeeding are sensitive to new generation broadly neutralizing antibodies directed against quaternary and CD4-binding site epitopes. AIDS Res Hum Retroviruses 29:511-5
Valley-Omar, Ziyaad; Sibeko, Sengeziwe; Anderson, Jeffrey et al. (2012) CAPRISA 004 tenofovir microbicide trial: no impact of tenofovir gel on the HIV transmission bottleneck. J Infect Dis 206:35-40
Lee, Sook-Kyung; Potempa, Marc; Swanstrom, Ronald (2012) The choreography of HIV-1 proteolytic processing and virion assembly. J Biol Chem 287:40867-74
Sturdevant, Christa Buckheit; Dow, Anna; Jabara, Cassandra B et al. (2012) Central nervous system compartmentalization of HIV-1 subtype C variants early and late in infection in young children. PLoS Pathog 8:e1003094
Anderson, Jeffrey A; Archin, Nancie M; Ince, William et al. (2011) Clonal sequences recovered from plasma from patients with residual HIV-1 viremia and on intensified antiretroviral therapy are identical to replicating viral RNAs recovered from circulating resting CD4+ T cells. J Virol 85:5220-3
Watts, Joseph M; Dang, Kristen K; Gorelick, Robert J et al. (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460:711-6
Kitrinos, Kathryn M; Nelson, Julie A E; Resch, Wolfgang et al. (2005) Effect of a protease inhibitor-induced genetic bottleneck on human immunodeficiency virus type 1 env gene populations. J Virol 79:10627-37
Ngrenngarmlert, Warunee; Kwiek, Jesse J; Kamwendo, Deborah D et al. (2005) Measuring allelic heterogeneity in Plasmodium falciparum by a heteroduplex tracking assay. Am J Trop Med Hyg 72:694-701
Henderson, Gavin J; Hoffman, Noah G; Ping, Li Hua et al. (2004) HIV-1 populations in blood and breast milk are similar. Virology 330:295-303
Rybarczyk, Brian J; Montefiori, David; Johnson, Philip R et al. (2004) Correlation between env V1/V2 region diversification and neutralizing antibodies during primary infection by simian immunodeficiency virus sm in rhesus macaques. J Virol 78:3561-71

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