Multiplicity of human immunodeficiency virus infections in lymphoid tissue

Human immunodeficiency virus type 1 (HIV-1)-infected splenocytes in humans were recently shown to harbor three to four proviruses per cell on average (A. Jung et al., Nature 418:144, 2002). However, the mechanisms that lead to such extensive multiple infections are not understood. Here, we find by using mathematical analysis that two mechanisms quantitatively capture the distribution of proviral genomes in HIV-1-infected splenocytes, one where multiple genomes are acquired one at a time in a series of sequential infectious contacts of a target cell with free virions and infected cells, and the other where cell-to-cell transmission of multiple virions or genomes results from a single infectious contact of a target cell with an infected cell. The two mechanisms imply different genetic diversities of proviruses within an infected cell and therefore different rates of emergence of drug resistance via recombination.