Heterosexual transmission of HIV-1 remains the dominant mechanism by which the epidemic is sustained woridwide. In a majority of transmissions, infection is established by a single genetic variant (the transmitted founder, TF) from the quasispecies of the transmitting partner (TP), with evidence for reduced Env glycosylation relative to their chronic counterparts. This concept of selection of virus with traits that favor transmission has been supported by our recent studies of viruses in the genital tract (GT), but it remains to be determined what functional properties differentiate TF viruses from their transmitting partner counterparts We hypothesize that differences in TF virus proteins allow preferential infection of key cell types within the genital mucosa and through interactions with antigen presenting cells signal the influx of activated CD4 T cells that can home to gut tissues. In this context, we will generate and characterize full-length single HIV-1 TF virus genomes and genomes amplified from TP bloodand GT in 20 Rwandan and Zambian transmission pairs;determine their abilities to productively infect vaginal and cervical tissue explants, determine whether different cells are infected by donor and recipient viruses, investigate their ability to interact with alpha-4, beta-7 molecules on mucosal T-cells and to induce the release of cytokines in antigen presenting cells capable of signaling trafficking of relevant activated T-cell populations. Newly infected partners in couples infected by different strains of HIV-1, are at high risk for superinfection and subsequent virus recombination. Based on preliminary data, we hypothesize that susceptibility to superinfection is related to low levels of neutralizing antibodies immediately prior to superinfection and that studies of superinfection will inform on the nature of protection required for an effective vaccine. We will therefore determine the frequency, kinetics and the virologic/immunologic ramifications of HIV superinfection in this cohort, as well as determine whether specific immunologic defects, such as low levels of protective antibody contribute to susceptibility to superinfection. The results of these studies will yield novel information that is critical to the design and testing of globally effective vaccine candidates.

Public Health Relevance

The experimental approaches described in this proposal will enhance our understanding ofthe eariiest aspects of heterosexual transmission of HIV-1 and will yield novel information regarding natural immunity that is critical to the design and testing of globally effective HlV-1 vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sharma, Opendra K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Schools of Medicine
United States
Zip Code
Penezina, Oksana; Krueger, Neil X; Rodriguez-Chavez, Isaac R et al. (2014) Performance of a redesigned HIV Selectest enzyme-linked immunosorbent assay optimized to minimize vaccine-induced seropositivity in HIV vaccine trial participants. Clin Vaccine Immunol 21:391-8
Cavrois, Marielle; Neidleman, Jason; Santiago, Mario L et al. (2014) Enhanced fusion and virion incorporation for HIV-1 subtype C envelope glycoproteins with compact V1/V2 domains. J Virol 88:2083-94
Claiborne, Daniel T; Prince, Jessica L; Hunter, Eric (2014) A restriction enzyme based cloning method to assess the in vitro replication capacity of HIV-1 subtype C Gag-MJ4 chimeric viruses. J Vis Exp :
Carlson, Jonathan M; Schaefer, Malinda; Monaco, Daniela C et al. (2014) HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science 345:1254031
Basu, Debby; Xiao, Peng; Ende, Zachary et al. (2014) Low antibody-dependent cellular cytotoxicity responses in Zambians prior to HIV-1 intrasubtype C superinfection. Virology 462-463:295-8
Deymier, Martin J; Claiborne, Daniel T; Ende, Zachary et al. (2014) Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning. Virology 468-470:454-61
Murphy, Megan K; Yue, Ling; Pan, Ruimin et al. (2013) Viral escape from neutralizing antibodies in early subtype A HIV-1 infection drives an increase in autologous neutralization breadth. PLoS Pathog 9:e1003173
Yue, Ling; Prentice, Heather A; Farmer, Paul et al. (2013) Cumulative impact of host and viral factors on HIV-1 viral-load control during early infection. J Virol 87:708-15
Boeras, Debrah I; Luisi, Nicole; Karita, Etienne et al. (2011) Indeterminate and discrepant rapid HIV test results in couples' HIV testing and counselling centres in Africa. J Int AIDS Soc 14:18
Price, Matt A; Wallis, Carole L; Lakhi, Shabir et al. (2011) Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa. AIDS Res Hum Retroviruses 27:5-12

Showing the most recent 10 out of 18 publications