Genetic drift and within-host metapopulation dynamics of HIV-1 infection

doi:10.1073/pnas.131056998

Genetic drift and within-host metapopulation dynamics of HIV-1 infection

^*Department of Pathology, University of California, San Diego, CA 92103; ^‡Unité de Rétrovirologie Moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France; and ^§Centre for HIV Research, University of Edinburgh, Edinburgh EH9 3JN, Scotland

Edited by Simon A. Levin, Princeton University, Princeton, NJ, and approved April 11, 2001 (received for review February 5, 2001)

Abstract

Most HIV replication occurs in solid lymphoid tissue, which has prominent architecture at the histological level, which separates groups of productively infected CD4⁺ cells. Nevertheless, current population models of HIV assume panmixis within lymphoid tissue. We present a simple “metapopulation” model of HIV replication, where the population of infected cells is comprised of a large number of small populations, each of which is established by a few founder viruses and undergoes turnover. To test this model, we analyzed viral genetic variation of infected cell subpopulations within the spleen and demonstrated the action of founder effects as well as significant variation in the extent of genetic differentiation between subpopulations among patients. The combination of founder effects and subpopulation turnover can result in an effective population size much lower than the actual population size and may contribute to the importance of genetic drift in HIV evolution despite a large number of infected cells.

Footnotes

↵ † To whom reprint requests should be addressed at: Department of Pathology, School of Medicine, University of California at San Diego, UCSD Treatment Center, 150 W. Washington Street, Suite 100, San Diego, CA 92103. E-mail: sdfrost{at}ucsd.edu.
This paper was submitted directly (Track II) to the PNAS office.
↵ ‖ Wakeley, J., 8th Annual Discussion Meeting on HIV Dynamics and Evolution, Paris, April 2001.
↵ ** Wang, Y., Marra, C. M., Learn, G. H., Rodrigo, A. G., Collier, A. C., Coombs, R. W., He, X., Zhao, H., & Mullins, J. I., Abstract no. 307, 7th Conference of Retroviruses and Opportunistic Infections, San Francisco, January 2000.