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Journal of Virology, May 2002, p. 5271-5273, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5271-5273.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Liver Is a Major Organ for Clearing Simian Immunodeficiency Virus in Rhesus Monkeys

Linqi Zhang,1 Peter J. Dailey,2,{dagger} Agegnehu Gettie,1 Jim Blanchard,3 and David D. Ho1*

Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York 10016,1 Bayer Corporation, Emeryville, California 94608,2 Tulane Regional Primate Research Center, Covington, Louisiana 704333

Received 12 November 2001/ Accepted 29 January 2002

Infection with human or simian immunodeficiency virus (SIV) is characterized by the rapid turnover of both viral particles and productively infected cells. It has recently been reported that the clearance of SIV in vivo is exceedingly fast, with half-lives on the order of minutes. The underlying mechanism or site responsible for this rapid clearance, however, remains unknown. To investigate this issue, we chose to infuse infectious SIVmac239 grown from autologous peripheral blood mononuclear cells that were radioactively labeled by [35S]methionine and [35S]cysteine. This approach eliminates from the viral membrane alloantigens that may have a significant impact on viral clearance. In addition, this approach also permits identification of the sites of viral clearance by measuring the radioactive intensity, even if degradation of SIV RNA occurs in tissues. We now report that the half-life of infused SIV in blood is extremely close to estimates from a previous study, in which unlabeled SIV grown in a heterologous cell line was used. The allogeneic effect due to the presence of human antigens on the surfaces of virions may, therefore, play a minimal role in the high rate of virion clearance. Moreover, close to 30% of infused radioactivity was found in the liver and measureable amounts were detected in the lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a significant proportion of infused virus in the liver suggests that viral clearance from circulation is mediated by a common, nonspecific mechanism, such as the phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions may pose a major obstacle for gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, 455 First Ave., 7th Floor, New York, NY 10016. Phone: (212) 448-5000. Fax: (212) 725-1126. E-mail: dho{at}adarc.org.

{dagger} Present address: Chiron Corporation, Emeryville, CA 94608.

Journal of Virology, May 2002, p. 5271-5273, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5271-5273.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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