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Journal of Virology, April 2005, p. 4886-4895, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4886-4895.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Retroviral Recombination In Vivo: Viral Replication Patterns and Genetic Structure of Simian Immunodeficiency Virus (SIV) Populations in Rhesus Macaques after Simultaneous or Sequential Intravaginal Inoculation with SIVmac239{Delta}vpx/{Delta}vpr and SIVmac239{Delta}nef

Eun-Young Kim,1 Marc Busch,2,3 Kristina Abel,2,3 Linda Fritts,2,3 Patty Bustamante,1 Jenny Stanton,1 Ding Lu,2,3 Samuel Wu,1 Jenny Glowczwskie,1 Tracy Rourke,2,3 Derek Bogdan,1 Mike Piatak Jr.,4 Jeffrey D. Lifson,4 Ronald C. Desrosiers,5 Steven Wolinsky,1 and Christopher J. Miller2,3,6*

Division of Infectious Diseases, The Feinberg School of Medicine at Northwestern University, Chicago, Illinois,1 Center for Comparative Medicine,2 California National Primate Research Center,3 Division of Infectious Diseases, School of Medicine, University of California, Davis, Davis, California,6 AIDS Vaccine Program, SAIC Frederick, Inc., NCI—Frederick, Frederick, Maryland,4 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts5

Received 4 August 2004/ Accepted 24 November 2004

To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239{Delta}vpx/{Delta}vpr and SIVmac239{Delta}nef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239{Delta}vpx/{Delta}vpr and then with SIVmac239{Delta}nef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239{Delta}nef when plasma SIVmac239{Delta}vpx/{Delta}vpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239{Delta}nef, and then with SIVmac239{Delta}vpx/{Delta}vpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.

* Corresponding author. Mailing address: UC Davis, CNPRC, One Shields Ave., Davis, CA 95616. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: cjmiller{at}ucdavis.edu.

Journal of Virology, April 2005, p. 4886-4895, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4886-4895.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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