EXCEED THE SPACE PROVIDED. In order to develop strategiesto prevent the spread of HIV-1, it is important to identify and characterize the viruses that are transmitted, particularly in high incidence areas. These analyses may illuminate the properties of the virus that determine its fitness for transmission, define the earliest target cells for virus replication, and may advance our understanding of the mechanisms of transmission. Moreover, it is likely that we can develop a better understanding of the virus-host cell interactions that influence HIV-1 pathogenesis if the clinical course of HIV-1 infection is specifically examined in relation to the virus that infects the host. Much of our current understanding of HIV-1*transmission and pathogenesis derives from studies of predominantly male cohorts in North America and Europe who are infected with subtype B HIV-1. In Africa, where the majority of HIV-1 infections and associated deaths are occurring, there.are multiple genetic subtypes of HIV-1, and subtype B is relatively uncommon. Thus, it is critical that the results of existing studies not be generalized to African populations, particularly when considering interventions to limit the spread or pathogenesis of HIV-1 infections. We have found that the majority of women in Africa are infected with a complex virus population, whereas African men and a minority of African women are infected by only a single virus variant. In contrast, previous studies of North American and European cohorts have consistently shown that only a single virus is transmitted. We hypothesize that the complex viruses that are transmitted to women in Africa may have distinct phenotypic or immunogenic properties that will influence disease progression: To address this, .we will ask whether infection that is initiated by a complex virus population will elicit a broader humoral immune response, and we will determine how the complexity of the infecting virus affects plasma and mucosal viral load and disease progression. In the course of the proposed studies, we will also determine if viral subtypes in Africa differ in their replication or pathogenic properties. We hypothesize that the viral subtype, the genetic complexity and/or the phenotype of the viral strain that infect the host will influence both systemic and mucosal virus replication, which in turn will influence progression to AIDS. The proposed combination of natural history studies and analyses of virus-host cell interactions will be focused on African women infected with non subtype B HIV-1 because this population represents approximately one third of all HIV-1 infections worldwide, yet almost nothing is known regarding HIV-1 pathogenesis in these individuals. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI038518-12
Application #
6909953
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sharma, Opendra K
Project Start
1995-09-15
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
12
Fiscal Year
2005
Total Cost
$601,374
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Williams, Katherine L; Wang, Bingjie; Arenz, Dana et al. (2018) Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire. Cell Rep 23:682-691
Roberts, Sarah T; Flaherty, Brian P; Deya, Ruth et al. (2018) Patterns of Gender-Based Violence and Associations with Mental Health and HIV Risk Behavior Among Female Sex Workers in Mombasa, Kenya: A Latent Class Analysis. AIDS Behav 22:3273-3286
Heffron, Renee; McClelland, R Scott; Balkus, Jennifer E et al. (2017) Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study. Lancet HIV 4:e449-e456
Ronen, Keshet; Dingens, Adam S; Graham, Susan M et al. (2017) Comprehensive Characterization of Humoral Correlates of Human Immunodeficiency Virus 1 Superinfection Acquisition in High-risk Kenyan Women. EBioMedicine 18:216-224
Doria-Rose, Nicole A; Altae-Tran, Han R; Roark, Ryan S et al. (2017) Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog 13:e1006148
LaCourse, Sylvia M; Deya, Ruth W; Graham, Susan M et al. (2017) Evaluation of the Isoniazid Preventive Therapy Care Cascade Among HIV-Positive Female Sex Workers in Mombasa, Kenya. J Acquir Immune Defic Syndr 76:74-81
Boyd, David F; Sharma, Amit; Humes, Daryl et al. (2016) Adapting SHIVs In Vivo Selects for Envelope-Mediated Interferon-? Resistance. PLoS Pathog 12:e1005727
McClelland, R Scott; Richardson, Barbra A; Cherutich, Peter et al. (2015) A 15-year study of the impact of community antiretroviral therapy coverage on HIV incidence in Kenyan female sex workers. AIDS 29:2279-86
Meyerson, Nicholas R; Sharma, Amit; Wilkerson, Gregory K et al. (2015) Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates. J Virol 89:8611-22
Cortez, Valerie; Wang, Bingjie; Dingens, Adam et al. (2015) The Broad Neutralizing Antibody Responses after HIV-1 Superinfection Are Not Dominated by Antibodies Directed to Epitopes Common in Single Infection. PLoS Pathog 11:e1004973

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