The clinical impact of HIV-1 dual infection has significant implications for understanding AIDS pathogenesis, virus transmission, and vaccine development. Dual infection can occur as a result of co-infection, wherein acquisition of two HIV-1 viral strains occurs during primary infection, or superinfection, wherein a second viral strain infects sometime after primary infection. Until recently, near simultaneous HIV-1 co-infection was thought to be the principle if not exclusive mode of dual infection. However, recent reports by several investigators, including our group, have shown that superinfection does indeed occur, and the circumstances under which this occurs may be instructive to understanding cellular niches for viruses and the interactions between the infecting strains. Furthermore, we have found that dual infection may be associated with more rapid disease progression. We propose in this continuing application to follow up our preliminary findings, expanding our studies of dual infection and adding considerable focus on rapid disease progression, including identification of host genes that impact these outcomes. Specifically, we propose to address the following specific aims and linked hypotheses using virologic, immunological and bioinformatics methodologies:
AIM 1 : Critically examine the link between dual HIV-1 infection and rapid disease progression. We will use population-based studies to assess the hypothesis that dual infection, when it occurs, is associated with accelerated disease progression.
AIM 2 : Determine the structure, interactions and replication fitness of dually infecting HIV-1 strains. We will test the hypotheses that viral strains in dually infected subjects differ in their replication fitness and capacity to infect distinct target cells, and that the types of viral interactions that occur is determined by the timing of infection with the second strain.
AIM 3 : Identify host genes that play a role in acquisition of dual infection and rapid disease progression. We will test the hypothesis that there is a strong host genetic component to susceptibility to multiple HIV infections, and that these genes are intimately associated with rapid disease progression. In summary, we will critically examine the link between dual HIV- 1 infection and rapid progression and determine viral and host genetic factors critical to that link.

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 #
5R37AI047734-07
Application #
7091462
Study Section
AIDS Immunology and Pathogenesis Study Section (AIP)
Program Officer
Huebner, Robin E
Project Start
2000-04-01
Project End
2010-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
7
Fiscal Year
2006
Total Cost
$523,047
Indirect Cost
Name
University of Washington
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Nakamura, Kyle J; Heath, Laura; Sobrera, Edwin R et al. (2017) Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures. Retrovirology 14:6
Dapp, Michael J; Kober, Kord M; Chen, Lennie et al. (2017) Patterns and rates of viral evolution in HIV-1 subtype B infected females and males. PLoS One 12:e0182443
Manocheewa, Siriphan; Lanxon-Cookson, Erinn C; Liu, Yi et al. (2015) Pairwise growth competition assay for determining the replication fitness of human immunodeficiency viruses. J Vis Exp :e52610
Liu, Yi; Rao, Ushnal; McClure, Jan et al. (2014) Impact of mutations in highly conserved amino acids of the HIV-1 Gag-p24 and Env-gp120 proteins on viral replication in different genetic backgrounds. PLoS One 9:e94240
Kahle, Erin; Campbell, Mary; Lingappa, Jairam et al. (2014) HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission: a multinational study among HIV-1 serodiscordant couples. AIDS 28:235-43
Moroni, Marco; Ghezzi, Silvia; Baroli, Paolo et al. (2014) Spontaneous control of HIV-1 viremia in a subject with protective HLA-B plus HLA-C alleles and HLA-C associated single nucleotide polymorphisms. J Transl Med 12:335
Castro, Erika; Zhao, Hong; Cavassini, Matthias et al. (2014) HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment. AIDS 28:1840-4
Herbeck, Joshua T; Mittler, John E; Gottlieb, Geoffrey S et al. (2014) An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load. PLoS Comput Biol 10:e1003673
Iyer, Shyamala; Bouzek, Heather; Deng, Wenjie et al. (2013) Quality score based identification and correction of pyrosequencing errors. PLoS One 8:e73015
Dobrowsky, Terrence M; Rabi, S Alireza; Nedellec, Rebecca et al. (2013) Adhesion and fusion efficiencies of human immunodeficiency virus type 1 (HIV-1) surface proteins. Sci Rep 3:3014

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