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Journal of Virology, January 2008, p. 321-334, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01094-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparison of Plasma Viremia and Antibody Responses in Macaques Inoculated with Envelope Variants of Single-Cycle Simian Immunodeficiency Virus Differing in Infectivity and Cellular Tropism

Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102,¹ AIDS Vaccine Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702,² Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115,³ Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,⁴ Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15238⁵

Received 21 May 2007/ Accepted 4 October 2007

Molecular differences in the envelope glycoproteins of human immunodeficiency virus type 1 and simian immunodeficiency virus (SIV) determine virus infectivity and cellular tropism. To examine how these properties contribute to productive infection in vivo, rhesus macaques were inoculated with strains of single-cycle SIV (scSIV) engineered to express three different envelope glycoproteins with full-length (TM_open) or truncated (TM_stop) cytoplasmic tails. The 239 envelope uses CCR5 for infection of memory CD4⁺ T cells, the 316 envelope also uses CCR5 but has enhanced infectivity for primary macrophages, and the 155T3 envelope uses CXCR4 for infection of both naive and memory CD4⁺ T cells. Separate groups of six rhesus macaques were inoculated intravenously with mixtures of TM_open and TM_stop scSIV_mac239, scSIV_mac316, and scSIV_mac155T3. A multiplex real-time PCR assay specific for unique sequence tags engineered into each virus was then used to measure viral loads for each strain independently. Viral loads in plasma peaked on day 4 for each strain and were resolved below the threshold of detection within 4 to 10 weeks. Truncation of the envelope cytoplasmic tail significantly increased the peak of viremia for all three envelope variants and the titer of SIV-specific antibody responses. Although peak viremias were similar for both R5- and X4-tropic viruses, clearance of scSIV_mac155T3 TM_stop was significantly delayed relative to the other strains, possibly reflecting the infection of a CXCR4⁺ cell population that is less susceptible to the cytopathic effects of virus infection. These studies reveal differences in the peaks and durations of a single round of productive infection that reflect envelope-specific differences in infectivity, chemokine receptor specificity, and cellular tropism.

Published ahead of print on 17 October 2007.

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