This proposal and progress report are intended to continue the work started in R37 AI066998. In the next funding cycle, we plan to expand this work in three broad areas that are outlined below. Area #1. To define the molecular mechanisms responsible for the differences in the pattern of infected cells between SIV-infected SMs and SIV-infected macaques and/or HIV-infected humans. Area #2. To characterize the relationship between the specific pattern of infected cells observed in SIV- infected SMs and their ability to avoid the chronic Immune activation of pathogenic HIV/SIV infections. Area #3. To determine how the SM-specific pattern of infected cells results in different features of the virus reservoir under anti-retroviral therapy (ART). We believe that these studies will advance significantly our understanding of how naturally SIV-infected SMs are resistant to AIDS despite high viremia. We envision that answering this question will provide clues to AIDS pathogenesis in humans that will have ultimately an impact on the prevention and treatment of HIV infection.

Public Health Relevance

Sooty mangabeys do not progress to AIDS despite being naturally infected with SIV, a virus closely related to HIV. The proposed studies are aimed at understanding why the sooty mangabeys are able to remain healthy when infected with SIV. We believe that these studies will improve our comprehension of AIDS pathogenesis in humans and that this knowledge will ultimately translate in better prevention and therapies fnr thfi infection

Agency
National Institute of Health (NIH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37AI066998-13
Application #
8884717
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lawrence, Diane M
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
McGary, Colleen S; Silvestri, Guido; Paiardini, Mirko (2014) Animal models for viral infection and cell exhaustion. Curr Opin HIV AIDS 9:492-9
McGary, Colleen S; Cervasi, Barbara; Chahroudi, Ann et al. (2014) Increased stability and limited proliferation of CD4+ central memory T cells differentiate nonprogressive simian immunodeficiency virus (SIV) infection of sooty mangabeys from progressive SIV infection of rhesus macaques. J Virol 88:4533-42
Cartwright, Emily K; McGary, Colleen S; Cervasi, Barbara et al. (2014) Divergent CD4+ T memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections. J Immunol 192:4666-73
Chahroudi, Ann; Cartwright, Emily; Lee, S Thera et al. (2014) Target cell availability, rather than breast milk factors, dictates mother-to-infant transmission of SIV in sooty mangabeys and rhesus macaques. PLoS Pathog 10:e1003958
Letko, Michael; Silvestri, Guido; Hahn, Beatrice H et al. (2013) Vif proteins from diverse primate lentiviral lineages use the same binding site in APOBEC3G. J Virol 87:11861-71
Francella, Nicholas; Gwyn, Sarah E; Yi, Yanjie et al. (2013) CD4+ T cells support production of simian immunodeficiency virus Env antibodies that enforce CD4-dependent entry and shape tropism in vivo. J Virol 87:9719-32
Bosinger, Steven E; Johnson, Zachary P; Folkner, Kathryn A et al. (2013) Intact type I Interferon production and IRF7 function in sooty mangabeys. PLoS Pathog 9:e1003597
Evans, David T; Silvestri, Guido (2013) Nonhuman primate models in AIDS research. Curr Opin HIV AIDS 8:255-61
Elliott, Sarah T C; Riddick, Nadeene E; Francella, Nicholas et al. (2012) Cloning and analysis of sooty mangabey alternative coreceptors that support simian immunodeficiency virus SIVsmm entry independently of CCR5. J Virol 86:898-908
Vanderford, Thomas H; Slichter, Chloe; Rogers, Kenneth A et al. (2012) Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Blood 119:5750-7

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