This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Human Immunodeficiency Virus (HIV) infection is associated with a progressive depletion of CD4+ T-cells whose extent predicts development of AIDS. Recently, it was shown that pathogenic HIV and simian immunodeficiency virus (SIV) infections of humans and macaques, respectively, are associated with an early, severe and largely irreversible loss of memory CD4+ T-cells in mucosal tissues. As such, a model has been proposed whereby this loss of mucosal CD4+ T-cells is a key determinant of progression to AIDS. Important insights into the pathogenesis of HIV infection have been provided by studies of non-pathogenic SIV infection of natural hosts, such as the sooty mangabey. In marked contrast to pathogenic lentiviral infections, natural SIV infection of mangabeys is not associated with an AIDS-like disease despite many years of infection with a highly replicating virus. The absence of disease in mangabeys has been attributed to the preservation of peripheral CD4+ T-cell homeostasis. Here we show that, in fact, both chronic 'natural' and acute 'experimental' SIV infections of mangabeys are characterized by a severe depletion of memory CD4+ T-cells from the intestinal and respiratory mucosa. However, in contrast to pathogenic HIV/SIV infections, the depletion of MALT CD4+ T-cells in mangabeys occurs in the context of low levels of immune activation and can be reverted by suppressing virus replication. In all, these results indicate that a profound depletion of MALT-associated CD4+ Tcells is not sufficient per se to induce disease progression in a natural host, thus emphasizing the role of other immunological abnormalities (e.g., chronic immune activation and dysfunction of non-CD4+ cells) in the pathogenesis of AIDS. These data provide a rationale for exploring new, immune-based approaches, in addition to standard antiretroviral therapy, in the clinical management of HIV-infected patients.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-46
Application #
7562368
Study Section
Special Emphasis Panel (ZRR1-CM-9 (01))
Project Start
2007-05-01
Project End
2008-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
46
Fiscal Year
2007
Total Cost
$71,639
Indirect Cost
Name
Tulane University
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

Showing the most recent 10 out of 352 publications