Lentiviral infection (Human Immunodeficiency Virus in humans) and the progression to AIDS are associated with chronic generalized activation and dysfunction of the immune system thought to drive pathogenesis. To determine the initiation of chronic immune activation, we recently studied acute lentiviral infection in two species of nonhuman primate;African green monkeys (AGM), resistant to the development of AIDS, and pigtailed macaques (PM), susceptible to the development of AIDS. We found that the earliest determinant of resistance or susceptibility to disease progression was the kinetic of the early innate antiviral response characterized by IFNa production: IFNa production was initiated in both species and remained elevated in PM, but was rapidly quenched in AGM. We hypothesize that this differential acute response to SIV infection is due to inherent differences in the detection of lentiviruses by the innate immune system in AGM and PM. This proposal investigates the mechanisms of lentiviral detection in the absence of infection in the AGM and PM as well as investigating the relationship between innate antiviral responses and the lack of disease in populations of HIV controllers.

Public Health Relevance

HIV infection causes widespread persistent inflammation that leads to the progressive loss of function in the immune system and the onset of AIDS. This proposal investigates the mechanisms of persistent inflammation during HIV infection with the goal of defining targets for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI091534-01
Application #
8012446
Study Section
Special Emphasis Panel (ZRG1-AARR-H (22))
Program Officer
Embry, Alan C
Project Start
2010-08-01
Project End
2013-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
1
Fiscal Year
2010
Total Cost
$50,474
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dunham, Richard M; Vujkovic-Cvijin, Ivan; Yukl, Steven A et al. (2014) Discordance between peripheral and colonic markers of inflammation during suppressive ART. J Acquir Immune Defic Syndr 65:133-41
Vujkovic-Cvijin, Ivan; Dunham, Richard M; Iwai, Shoko et al. (2013) Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 5:193ra91
Dunham, Richard M; Gordon, Shari N; Vaccari, Monica et al. (2013) Preclinical evaluation of HIV eradication strategies in the simian immunodeficiency virus-infected rhesus macaque: a pilot study testing inhibition of indoleamine 2,3-dioxygenase. AIDS Res Hum Retroviruses 29:207-14