Early Events Following Oral Transmission of Simian Immunodeficiency Virus: From Viral Entry to Host Immune Response

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Title: Early Events Following Oral Transmission of Simian Immunodeficiency Virus: From Viral Entry to Host Immune Response
Author: Milush, Jeffrey Martin
Abstract: Approximately 40 million people worldwide are infected with HIV , the causative agent of AIDS . The primary mode of HIV transmission (75 % of all transmissions ) between individuals occurs across mucosal tissues (vaginal , rectal , oral ) . The goal of this thesis was to assess the virologic and immunologic events following oral inoculation of macaques with Simian Immunodeficiency Virus (SIV ) and correlate these findings with disease progression . To assess the virologic events involving viral entry and spread , macaques were orally inoculated with SIV and necropsied at early times post -infection (days 1 - 14 ) . These studies were the first to identify the preferential entry sites for the virus as the oral and esophageal mucosa , as well as the tonsils . Furthermore , SIV rapidly disseminated to peripheral lymph nodes resulting in systemic infection by 2 to 4 days post -infection . The rapidity with which SIV spreads throughout the lymphatics indicates a major obstacle for a vaccine recall immune response to eliminate infected cells prior to dissemination . Analyses of immunologic events through the assessment of mucosal innate immune gene expression , as well as the initiation of the adaptive immune response , were undertaken in a second group of SIV orally inoculated macaques . Two hypotheses were proposed : 1 ) An innate mucosal immune response at the site of entry (oral mucosa ) would result in the induction of a timely SIV -specific adaptive immune response ; and 2 ) Maintaining a healthy mucosal barrier during chronic infection would prevent the onset of opportunistic infections . My data support hypothesis one , as during early times post -infection (2 - 21 days ) , gingival mucosal innate response gene expression correlated with the ability toinduce timely SIV antibodies and reduce plasma viral loads . In addition , my data assessing events during chronic infection (day 70 ) indicated an association between elevated expression of mucosal innate response genes , particularly chemokines , with an absence of opportunistic infections , thus supporting hypothesis two . From these studies assessing viral and immune correlates of SIV transmission , I conclude that vaccines capable of inducing high titer neutralizing antibodies at the mucosa , as well as increased mucosal innate immune responses , will be most efficacious in preventing mucosal HIV transmissions .
URI: http : / /hdl .handle .net /2152 .5 /696
Date: 2005-08-11

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Early Events Following Oral Transmission of Simian Immunodeficiency Virus: From Viral Entry to Host Immune Response. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /696 .

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