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J. Virol. doi:10.1128/JVI.00042-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mucosal Innate Immune Response Associated With A Timely Humoral Immune Response And Slower Disease Progression Following Oral Transmission Of SIV In Rhesus Macaques

Dept. of Internal Medicine, University of Texas Southwestern Medical Center, Dallas TX 75390; University of Pittsburgh, Pittsburgh PA, California National Primate Research Center, University of California, Davis CA; Tulane National Primate Research Center, Covington LA, Tulane Health Sciences Center, Tulane University, New Orleans LA

^* To whom correspondence should be addressed. Email: Donald.Sodora{at}UTSouthwestern.edu.

	Abstract

Mucosal transmission is the predominant mode of HIV infection worldwide, and the mucosal innate interferon response represents an important component of the earliest host response to the infection. Our goal here was to assess the changes in mRNA expression of innate mucosal genes following oral simian immunodeficiency virus (SIV) inoculation of rhesus macaques (Macaca mulatta) that were followed throughout their course of disease progression. SIV plasma viral load was highest in the macaque that progressed rapidly to simian AIDS (99 days) and lowest in the macaque that progressed more slowly (> 700 days). The mRNA levels of 6 innate/effector genes at the oral mucosa indicated that slower disease progression was associated with increased expression of these genes. This distinction was most evident when comparing the slowest progressing macaque to the intermediate and rapid progressors: interferon alpha and gamma, the antiviral interferon stimulated gene (OAS), and chemokines CXCL9 and CXCL10 in the slow progressor were elevated at each of the three oral mucosal biopsy timepoints examined (day 2-4, 14-21, and 70 post-infection). In contrast, the more rapidly progressing macaques demonstrated elevated levels of these cytokine/chemokine mRNA levels at lymph nodes, coincident with decreased levels at the mucosal sites and a decreased ability to elicit an effective anti-SIV antibody response. These data provide evidence that a robust mucosal innate/effector immune response is beneficial following lentiviral exposure, however, it is likely that the anatomical location and timing of the response needs to be coordinated to permit an effective immune response able to delay progression to simian AIDS.

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