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Journal of Virology, April 2009, p. 3288-3297, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02423-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection{triangledown}

Zhong-Min Ma,1,2 Mars Stone,1,2 Mike Piatak Jr.,3 Becky Schweighardt,4 Nancy L. Haigwood,5 David Montefiori,6 Jeffrey D. Lifson,3 Michael P. Busch,7,8 and Christopher J. Miller1,2,9*

California National Primate Research Center,1 Center for Comparative Medicine,2 Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California 95616,9 AIDS and Cancer Virus Program, Science Applications International Corporation—Frederick, Inc., National Cancer Institute, Frederick, Maryland,3 Monogram Biosciences, Inc., South San Francisco, California,4 Oregon National Primate Research Center, Oregon Health Sciences University, Beaverton, Oregon 97006,5 Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710,6 Blood Systems Research Institute,7 Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 941188

Received 24 November 2008/ Accepted 2 January 2009

To define the ratio of simian immunodeficiency virus (SIV) RNA molecules to infectious virions in plasma, a ramp-up-stage plasma pool was made from the earliest viral RNA (vRNA)-positive plasma samples (collected approximately 7 days after inoculation) from seven macaques, and a set-point-stage plasma pool was made from plasma samples collected 10 to 16 weeks after peak viremia from seven macaques; vRNA levels in these plasma pools were determined, and serial 10-fold dilutions containing 1 to 1,500 vRNA copies/ml were made. Intravenous (i.v.) inoculation of a 1-ml aliquot of diluted ramp-up-stage plasma containing 20 vRNA copies infected 2 of 2 rhesus macaques, while for the set-point-stage plasma, i.v. inoculation with 1,500 vRNA copies was needed to transmit infection. Further, when the heat-inactivated set-point-stage plasma pool was mixed with ramp-up-stage virions, infection of inoculated macaques was blocked. Notably, 2 of 2 animals inoculated with 85 ml of a pre-ramp-up plasma pool containing <3 SIV RNA copies/ml developed SIV infections characterized by high levels of viral replication, demonstrating that "vRNA-negative" plasma collected from macaques in the pre-ramp-up stage is infectious. Furthermore, there is a high ratio of infectious virions to total virions in ramp-up-stage plasma (between 1:1 and 1:10) and a lower ratio in set-point-stage plasma (between 1:75 and 1:750). Heat-inactivated chronic-stage plasma can "neutralize" the highly infectious ramp-up-stage virions. These findings have implications for the understanding of the natural history of SIV and human immunodeficiency virus infection and transmission.

* Corresponding author. Mailing address: California National Primate Research Center, University of California at Davis, One Shields Ave., Davis, CA 95616. Phone: (530) 752-1229. Fax: (530) 754-4411. E-mail: cjmiller{at}ucdavis.edu

{triangledown} Published ahead of print on 7 January 2009.

Journal of Virology, April 2009, p. 3288-3297, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02423-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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