Abstract

Asian macaques develop an AIDS-like disease upon infection with lentiviruses that endemically infect African nonhuman primates. However, African monkeys fail to develop disease despite persistent and life-long infection with the same viruses. A clear understanding of the mechanisms responsible for the natural resistance of African monkeys to lentivirus-induced disease might support current strategies to develop AIDS vaccines or provide insight into new treatment modalities for HIV infection. In this proposal, we will utilize the infection of two African green monkey species infected with SIVagm to study this phenomenon. Using the models of monoclonal antibody-induced depletion of CD8+ lymphocytes and B cells which we developed previously, we will assess the role of adaptive immune responses to the natural resistance to disease seen in these species. Specifically, we will: 1. Determine the role of adaptive immune responses mediated by CD8+ lymphocytes in controlling SIVagm viremia and disease progression in African green monkeys. 2. Determine the role of humoral immune responses in affecting the course of the same infections by depletion of B lymphocytes. 3. Assess whether abolishing both cellular and humoral adaptive immune responses will affect the course of SIVagm infection of African green monkeys. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI065335-02
Application #
7189844
Study Section
AIDS Immunology and Pathogenesis Study Section (AIP)
Program Officer
Finzi, Diana
Project Start
2006-03-01
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
2
Fiscal Year
2007
Total Cost
$656,362
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Keating, Sheila M; Heitman, John W; Wu, Shiquan et al. (2016) Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates. J Virol 90:10339-10350
Couturier, Jacob; Hutchison, Alexander T; Medina, Miguel A et al. (2014) HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies. Virology 462-463:175-88
Ho, Carrie; Wu, Steven; Amos, Joshua D et al. (2013) Transient compartmentalization of simian immunodeficiency virus variants in the breast milk of african green monkeys. J Virol 87:11292-9
Schmitz, Joern E; Ma, Zhong-Min; Hagan, Emily A et al. (2012) Memory CD4(+) T lymphocytes in the gastrointestinal tract are a major source of cell-associated simian immunodeficiency virus in chronic nonpathogenic infection of African green monkeys. J Virol 86:11380-5
Handley, Scott A; Thackray, Larissa B; Zhao, Guoyan et al. (2012) Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151:253-66
Hutchison, A T; Schmitz, J E; Miller, C J et al. (2011) Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates. J Med Primatol 40:414-26
Wilks, Andrew B; Perry, James R; Ehlinger, Elizabeth P et al. (2011) High cell-free virus load and robust autologous humoral immune responses in breast milk of simian immunodeficiency virus-infected african green monkeys. J Virol 85:9517-26
Klatt, Nichole R; Shudo, Emi; Ortiz, Alex M et al. (2010) CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS Pathog 6:e1000747
Sodora, Donald L; Allan, Jonathan S; Apetrei, Cristian et al. (2009) Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts. Nat Med 15:861-5
Schmitz, Jörn E; Zahn, Roland C; Brown, Charles R et al. (2009) Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys. PLoS Pathog 5:e1000691

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