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Session 52 Poster Session Pathogenesis Studies in Animal Models Session Time: 4:30-6:30 pm Room 4E-F

328-W. Liver Is a Major Organ for Clearing SIV Particles in Rhesus Monkeys L. Zhang*1, P. J. Dailey2, A. Gettie1, and D. Ho1 1Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY and 2Bayer Corp., Emeryville, CA Background: Infection by HIV or SIV is characterized by the rapid turnover of both viral particles and productively infected cells. Using the SIV/rhesus macaque model, it has been reported that the clearance of exogenously infused SIV particles is exceedingly fast in vivo, with half-lives on the order of minutes. The anatomical site(s) responsible for this rapid clearance, however, remains unknown. Methods: To investigate this issue, we infused infectious SIVmac239 virions into 1 monkey, whose PBMC were used to grow the virus stock in the presence of 35S-labeled methionine and cysteine. By using autologous PBMC to prepare each viral stock, we eliminated alloantigens from being assembled onto the viral surface, thereby avoiding their contribution to viral clearance. In addition, this approach also permitted the identification of the anatomical site(s) of viral clearance by tracking the radioactivity in various body organs and tissues that were obtained hours later at autopsy, even after degradation of SIV RNA has occurred. Results: In this study, we found that the half-life of infused SIV virion in blood is extremely close to our previous estimate (half-life of 4 minutes) for unlabeled SIV particles produced in a heterologous cell line. Thus, the presence of alloantigens on the virion surface does not play a major role in the rapid particle clearance from blood. In addition, close to 30% of the radiolabeled SIV virions infused were detected in the liver, with only small quantities found in lung (5.4%), lymph nodes (3.0%), and spleen (0.4%). However, much of the infused radioactivity was unaccounted for. Conclusions: The detection in the liver of a significant proportion of the infused virions is consistent with findings from the 1960s that show that a variety of viruses other than HIV/SIV are cleared by non-specific phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions could pose a major obstacle for those pursuing gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.

©2002 9th Conference on Retroviruses and Opportunistic Infections