Although substantial progress has been made on understanding the mechanism of HIV-1 entry into cells, much less is known about the process of virus transmission in vivo. What structural and functional properties of the viral Env protein differentiate the transmitted virus from other variants and facilitate transmission across mucosal surfaces? In this application, we propose to analyze HIV-1 virus populations isolated from both the donor and recipient immediately following a transmission event in unique cohorts of discordant couples in Rwanda and Zambia. These studies will provide a unique opportunity to investigate the virologic determinants of heterosexual transmission specified by the variable regions of gp120 in biologically relevant viral envelope genes using samples from large, well-characterized discordant couple cohorts that represent two predominant clades (A and C) of HIV-1. Our hypothesis is that extensions and heavy glycosylation of the first two variable regions of gp120 (V1V2) confer a selective advantage to the virus during long-term infection of an individual but that these same changes are disadvantageous during viral transmission, when variants with different modifications in V1V2 have a selective advantage. Specifically we will: 1. Determine the amino acid sequence of the V1-V5 region of gp120 in virus isolated from donor and recipient at the time of acute infection in order to identify sequence variants selected during transmission; 2. Determine whether the selection of viral variants reflects the population of virus present in the genital fluids of the donor or a biological restriction of the transmission process; 3. Compare the heterogeneity of virus present in recipients at the time of acute infection by gender and by virus clade; and 4. Compare the functional properties of viral variants present in the donor and recipient at the time of acute infection. The results of these studies will enhance our understanding of the heterosexual transmission process and will yield novel information that is critical to the design and testing of globally effective vaccine candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051231-05
Application #
6866380
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Sharma, Usha K
Project Start
2002-03-15
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
5
Fiscal Year
2005
Total Cost
$868,993
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Connolly, Sarah; Wall, Kristin M; Tang, Jianming et al. (2018) Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression. Virology 525:132-142
Wall, Kristin M; Inambao, Mubiana; Kilembe, William et al. (2018) HIV testing and counselling couples together for affordable HIV prevention in Africa. Int J Epidemiol :
Haddad, Lisa B; Wall, Kristin M; Kilembe, William et al. (2018) Bacterial vaginosis modifies the association between hormonal contraception and HIV acquisition. AIDS 32:595-604
Joseph Davey, Dvora Leah; Wall, Kristin M; Kilembe, William et al. (2018) Difficult decisions: Evaluating individual and couple-level fertility intentions and HIV acquisition among HIV serodiscordant couples in Zambia. PLoS One 13:e0189869
Joseph Davey, Dvora L; Wall, Kristin M; Kilembe, William et al. (2017) HIV Incidence and Predictors of HIV Acquisition From an Outside Partner in Serodiscordant Couples in Lusaka, Zambia. J Acquir Immune Defic Syndr 76:123-131
Wall, Kristin M; Kilembe, William; Vwalika, Bellington et al. (2017) Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994-2012. Int J Epidemiol 46:1593-1606
Monaco, Daniela C; Ende, Zachary; Hunter, Eric (2017) Virus-Host Gene Interactions Define HIV-1 Disease Progression. Curr Top Microbiol Immunol 407:31-63
Joseph Davey, Dvora; Kilembe, William; Wall, Kristin M et al. (2017) Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It? AIDS Behav 21:1892-1903
Wall, Kristin M; Kilembe, William; Haddad, Lisa et al. (2016) Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women. J Acquir Immune Defic Syndr 71:345-52
Wall, Kristin M; Kilembe, William; Vwalika, Bellington et al. (2016) Hormonal Contraceptive Use Among HIV-Positive Women and HIV Transmission Risk to Male Partners, Zambia, 1994-2012. J Infect Dis 214:1063-71

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