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Journal of Virology, April 2001, p. 3753-3765, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3753-3765.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Route of Simian Immunodeficiency Virus Inoculation Determines the Complexity but Not the Identity of Viral Variant Populations That Infect Rhesus Macaques

Jennifer L. Greenier,1 Christopher J. Miller,1,2,3 Ding Lu,1 Peter J. Dailey,4 Fabien X. Lü,1 Kevin J. Kunstman,5 Steven M. Wolinsky,5 and Marta L. Marthas1,2,*

California Regional Primate Research Center,1 Department of Veterinary Pathology, Microbiology and Immunology,2 and Center for Comparative Medicine,3 School of Veterinary Medicine, University of California, Davis, California 95616; Bayer Reference Laboratory, Emeryville, California 946084; and Department of Infectious Diseases, Northwestern University School of Medicine, Chicago, Illinois 606115

Received 22 September 2000/Accepted 12 January 2001

A better understanding of the host and viral factors associated with human immunodeficiency virus (HIV) transmission is essential to developing effective strategies to curb the global HIV epidemic. Here we used the rhesus macaque-simian immunodeficiency virus (SIV) animal model of HIV infection to study the range of viral genotypes that are transmitted by different routes of inoculation and by different types of viral inocula. Analysis of transmitted variants was undertaken in outbred rhesus macaques inoculated intravenously (IV) or intravaginally (IVAG) with a genetically heterogeneous SIVmac251 stock derived from a well-characterized rhesus macaque viral isolate. In addition, we performed serial IV and IVAG passage experiments using plasma from SIV-infected macaques as the inoculum. We analyzed the V1-V2 region of the SIV envelope gene from virion-associated RNA in plasma from infected animals by the heteroduplex mobility assay (HMA) and by DNA sequence analysis. We found that a more diverse population of SIV genetic variants was present in the earliest virus-positive plasma samples from all five IV SIVmac251-inoculated monkeys and from two of five IVAG SIVmac251-inoculated monkeys. In contrast, we found a relatively homogeneous population of SIV envelope variants in three of five monkeys inoculated IVAG with SIVmac251 stock and in two monkeys infected after IVAG inoculation with plasma from an SIV-infected animal. In some IVAG-inoculated animals, the transmitted SIV variant was the most common variant in the inoculum. However, a specific viral variant in the SIVmac251 stock was not consistently transmitted by IVAG inoculation. Thus, it is likely that host factors or stochastic processes determine the specific viral variants that infect an animal after IVAG SIV exposure. In addition, our results clearly demonstrate that the route of inoculation is associated with the extent and breadth of the genetic complexity of the viral variant population in the earliest stages of systemic infection.

* Corresponding author. Mailing address: California Regional Primate Research Center, Hutchison Dr. and County Road 98, Davis, CA 95616-8542. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: mlmarthas{at}ucdavis.edu.

Journal of Virology, April 2001, p. 3753-3765, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3753-3765.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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