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144 SIV Clearance from an Infected Macaque: Role of Host Immunity and Post-Entry Cellular Factor
S. Than1, S. O'Neil2, R. Voltan3, B. Peng3, J. T. Safrit4, R. Woodward1, P. D. Markham1, Y. Edghill-Smith3, and M. Robert-Guroff*3
1Advanced BioScience Labs, Inc., Kensington, MD, USA; 2Yerkes Regional Primate Res. Ctr., Atlanta, GA, USA; 3NCI, Bethesda, MD, USA; and 4Emory Univ. Sch. of Med., Atlanta, GA
Background: Rhesus macaque 359L, resistant to mucosal SIV infection, was viremic only at 2 weeks after a third intrarectal viral exposure and never seroconverted. In situ detection of SIV RNA suggested virus was sequestered in the intestinal lamina propria. Here we document viral clearance and investigate host resistance mechanisms.
Methods: Blood and lymph node cells of macaque 359L obtained 44 weeks after the 3rd SIV exposure were transfused into naïve macaque 828L. SIV infection was assessed by virus isolation, NASBA for SIV RNA, and serologic assay. Macaque 359L CD8 cells were depleted in vivo using OKT8F antibody. CD8 cells were monitored in blood and tissues by FACS and immunohistochemical techniques. Intermediate products of in vitro SIVmac251 reverse transcription in CD4 cells of macaque 359 and control macaques were evaluated by PCR.
Results: Macaque 828L was not infected by transfused macaque 359L cells. Further, a latent SIV reservoir in macaque 359L was not seen. Upon OKT8F treatment, blood CD8 cells dropped to and remained at <1% for 11 days until euthanasia. Necropsy tissues showed significant depletion of CD8 cells compared with predepletion levels. Lymph nodes, gut, brain, genital tract, and other major tissues were negative for SIV RNA at <200 copies. In vitro SIV replication intermediates in pre-SIV exposed 359L CD4 cells were decreased 100-fold compared with levels in control susceptible cells.
Conclusions: Initial resistance of macaque 359L to SIV infection is attributed to a post-entry block in replication. SIV clearance was likely further aided by low level cellular immunity induced by prior mucosal SIV exposures. A low viral burden due to greatly reduced SIV replication following transmission would allow more effective host control and eventual viral clearance. Identification of the putative cellular factor and assessment of its prevalence will be important for users of the macaque model, for potential therapy, and for further understanding viral reverse transcription.
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