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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
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
2016-03-01
Project End
2021-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
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
Chahroudi, Ann; Silvestri, Guido; Lichterfeld, Mathias (2015) T memory stem cells and HIV: a long-term relationship. Curr HIV/AIDS Rep 12:33-40
Elliott, Sarah T C; Wetzel, Katherine S; Francella, Nicholas et al. (2015) Dualtropic CXCR6/CCR5 Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabey Primary Lymphocytes: Distinct Coreceptor Use in Natural versus Pathogenic Hosts of SIV. J Virol 89:9252-61
Mir, Kiran D; Mavigner, Maud; Wang, Charlene et al. (2015) Reduced Simian Immunodeficiency Virus Replication in Macrophages of Sooty Mangabeys Is Associated with Increased Expression of Host Restriction Factors. J Virol 89:10136-44
D'arc, Mirela; Ayouba, Ahidjo; Esteban, Amandine et al. (2015) Origin of the HIV-1 group O epidemic in western lowland gorillas. Proc Natl Acad Sci U S A 112:E1343-52
Barbian, Hannah J; Decker, Julie M; Bibollet-Ruche, Frederic et al. (2015) Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. MBio 6:
Cohn, Lillian B; Silva, Israel T; Oliveira, Thiago Y et al. (2015) HIV-1 integration landscape during latent and active infection. Cell 160:420-32
Sauter, Daniel; Hotter, Dominik; Van Driessche, Benoît et al. (2015) Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins. Cell Rep 10:586-99
McGary, Colleen S; Silvestri, Guido; Paiardini, Mirko (2014) Animal models for viral infection and cell exhaustion. Curr Opin HIV AIDS 9:492-9
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
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

Showing the most recent 10 out of 29 publications