Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques

doi:10.1073/pnas.0707449104

Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques

^†Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016;
^‡National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700 B Rockledge Drive, MSC 7609, Bethesda, MD 20892;
^§Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545; and
^¶AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100730, China

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved October 15, 2007 (received for review August 7, 2007)

Abstract

A single-cycle simian immunodeficiency virus (scSIV) that undergoes only one round of infection and replication was constructed to calculate the total number of virons produced by an SIV-infected cell in vivo. Four Mamu-A*01 rhesus macaques were inoculated on two occasions 11 weeks apart with the scSIV by ex vivo infection and i.v. reinfusion of autologous cells. After each inoculation, plasma viral loads peaked between 1 and 2.5 days and then declined exponentially in one or two phases to below detection limits within 2 weeks. Although higher levels of SIV-specific cytotoxic T lymphocytes and modest increases in antibody responses were observed for each animal after the second inoculation, decay rates of the infected cells were only minimally affected. Analyzing the viral load data with a mathematical model, the in vivo viral burst size averaged 4.0 × 10⁴ and 5.5 × 10⁴ virions per cell for the first and second inoculations, respectively, with no significant difference between the two inoculations. This estimate, in conjunction with our prior understanding of other quantitative viral and cellular parameters during SIV and HIV infection, provides critical insights into the dynamic process of viral production and its interplay with the infected host in vivo.

Footnotes

^‖To whom correspondence should be addressed. E-mail: lzhang{at}adarc.org
Author contributions: D.D.H. and L.Z. designed research; H.Y.C. and L.Z. performed research; H.Y.C., M.D.M., A.S.P., D.D.H., and L.Z. analyzed data; and H.Y.C., M.D.M., A.S.P., and L.Z. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.