This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project focuses on understanding the reasons why natural hosts for SIV infection, such as the sooty mangabeys (SMs), in striking contrast to HIV-infected individuals, are not susceptible to AIDS despite high viremia. We recently showed that CCR5 expression is significantly lower in central memory CD4+ T cells of SMs when compared to humans and macaques, and that this lower expression results in decreased susceptibility to SIV infection. This work is now submitted for publication. In addition, as part of the studies sponsored by R01-AI66998, we have made three novel observation that are all now published (see below). The first observation is that the conclusion of a five-years longitudinal survey of naturally SIV-infected SMs prompted us to realize that the infection is associated with a slow but progressive decline of CD4+ T cells without increasing viral load or immune activation. The second observation is that 5-7% of naturally SIV-infected SMs are homozygous for a 2bp deletion in the second extracellular loop of CCR5 that results in abrogated surface expression of thsi molecule. Interestingly, these rare CCR5 knock-out SMs are infected with SIV albeit at lower levels. These animals do not develop viruses using CXCR4, but other SIV co-receptors such as GPR-1 and GPR-15. The third observation is that, in naturally SIV-infected SMs, the level of autologous neutralizing antibodies is very low, and does not correlate with either viral load or CD4+ T cell loss. We believe that these data improve our understanding of the pathophysiology of SIV infection in SMs.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000165-51
Application #
8357469
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-08-01
Project End
2012-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
51
Fiscal Year
2011
Total Cost
$89,196
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Meng, Yuguang; Hu, Xiaoping; Zhang, Xiaodong et al. (2018) Diffusion tensor imaging reveals microstructural alterations in corpus callosum and associated transcallosal fiber tracts in adult macaques with neonatal hippocampal lesions. Hippocampus 28:838-845
Mylvaganam, Geetha H; Chea, Lynette S; Tharp, Gregory K et al. (2018) Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV. JCI Insight 3:
Kamara, Dennis M; Gangishetti, Umesh; Gearing, Marla et al. (2018) Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer's Disease. J Alzheimers Dis 62:1815-1826
Ploquin, Mickaƫl J; Casrouge, Armanda; Madec, Yoann et al. (2018) Systemic DPP4 activity is reduced during primary HIV-1 infection and is associated with intestinal RORC+ CD4+ cell levels: a surrogate marker candidate of HIV-induced intestinal damage. J Int AIDS Soc 21:e25144
Fonseca, Jairo A; McCaffery, Jessica N; Caceres, Juan et al. (2018) Inclusion of the murine IgG? signal peptide increases the cellular immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage vaccine. Vaccine 36:2799-2808
Tedesco, Dana; Thapa, Manoj; Chin, Chui Yoke et al. (2018) Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic ?? T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease. Gastroenterology 154:2178-2193
Robinson, Amy A; Abraham, Carmela R; Rosene, Douglas L (2018) Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience 40:31-47
Walker, Lary C (2018) Sabotage by the brain's supporting cells helps fuel neurodegeneration. Nature 557:499-500
Mascaro, Jennifer S; Rentscher, Kelly E; Hackett, Patrick D et al. (2018) Preliminary evidence that androgen signaling is correlated with men's everyday language. Am J Hum Biol 30:e23136
Forger, Nancy G; Ruszkowski, Elara; Jacobs, Andrew et al. (2018) Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques. Horm Behav 100:39-46

Showing the most recent 10 out of 912 publications