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Journal of Virology, November 2005, p. 13579-13586, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13579-13586.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

How Many Human Immunodeficiency Virus Type 1-Infected Target Cells Can a Cytotoxic T-Lymphocyte Kill?

Statistical Center for HIV and AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,¹ UCLA AIDS Institute, Department of Medicine, Department of Microbiology, Immunology and Molecular Genetics, David Greffen School of Medicine, UCLA, Los Angeles, California 90095,² Department of Medicine, University of Washington, Seattle, Washington 98101,³ Program in Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109⁴

Received 27 April 2005/ Accepted 26 July 2005

The antiviral role of CD8⁺ cytotoxic T lymphocytes (CTLs) in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. Specifically, the degree to which CTLs reduce viral replication by killing HIV-1-infected cells in vivo is not known. Here we employ mathematical models of the infection process and CTL action to estimate the rate that CTLs can kill HIV-1-infected cells from in vitro and in vivo data. Our estimates, which are surprisingly consistent considering the disparities between the two experimental systems, demonstrate that on average CTLs can kill from 0.7 to 3 infected target cells per day, with the variability in this figure due to epitope specificity or other factors. These results are compatible with the observed decline in viremia after primary infection being primarily a consequence of CTL activity and have interesting implications for vaccine design.

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