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

Most HIV replication occurs in solid lymphoid tissue, which has prominent a rchitecture at the histological level, which separates groups of productive ly infected CD4(+) cells. Nevertheless, current population models of HIV as sume panmixis within lymphoid tissue. We present a simple "metapopulation" model of HIV replication, where the population of infected cells is compris ed 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 analyz ed viral genetic variation of infected cell subpopulations within the splee n and demonstrated the action of founder effects as well as significant var iation in the extent of genetic differentiation between subpopulations amon g patients. The combination of founder effects and subpopulation turnover c an result in an effective population size much lower than the actual popula tion size and may contribute to the importance of genetic: drift in HIV evo lution despite a large number of infected cells.