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

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dc.contributor.advisor Sodora , Donald L . en
dc.creator Milush , Jeffrey Martin en
dc.date.accessioned 2010 -07 -12T18 :51 :23Z en
dc.date.accessioned 2014 -02 -19T22 :00 :47Z
dc.date.available 2010 -07 -12T18 :51 :23Z en
dc.date.available 2014 -02 -19T22 :00 :47Z
dc.date.issued 2005 -08 -11 en
dc.identifier.other en
dc.identifier.uri http : / /hdl .handle .net /2152 .5 /696 en
dc.description.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 . en
dc.format.medium Electronic en
dc.format.mimetype application /pdf en
dc.language.iso en en
dc.subject Disease Progression en
dc.subject Vaccination en
dc.subject Simian immunodeficiency virus en
dc.title Early Events Following Oral Transmission of Simian Immunodeficiency Virus : From Viral Entry to Host Immune Response en
dc.type.genre dissertation en
dc.type.material Text en
thesis.degree.name Doctor of Philosophy en
thesis.degree.level Ph .D . en
thesis.degree.discipline Molecular Microbiology en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.department en
dc.format.digitalOrigin born digital en
thesis.date.available 2006 -08 -11 en


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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