Majority of CD4 ⁺ T cells from peripheral blood of HIV-1–infected individuals contain only one HIV DNA molecule

Abstract

Neither the number of HIV-1 proviruses within individual infected cells in HIV-1–infected patients nor their genetic relatedness within individual infected cells and between cells and plasma virus are well defined. To address these issues we developed a technique to quantify and genetically characterize HIV-1 DNA from single infected cells in vivo. Analysis of peripheral blood CD4 + T cells from nine patients revealed that the majority of infected cells contain only one copy of HIV-1 DNA, implying a limited potential for recombination in virus produced by these cells. The genetic similarity between HIV populations in CD4 + T cells and plasma implies ongoing exchange between these compartments both early and late after infection.

Impaired immune evasion in HIV through intracellular delays and multiple infection of cells

“…The proviruses that were found in CD4 þ T cells of the peripheral blood were found to be genetically similar to the circulating virus in the plasma [19], indicating that they represent the replicating virus population. On the other hand, the majority of HIVinfected cells reside in lymph nodes and the spleen [49], but it remains unclear whether the multiply infected splenocytes in the study from Jung et al [11] represent productively infected cells that contribute to ongoing virus replication.…”

“…Given the discrepancy between the multiplicity of infection that has been found in the spleen [11] and the peripheral blood [19], we cannot clearly say how strong an effect of multiple-infected cells on immune escape in HIV is to be expected. The proviruses that were found in CD4 þ T cells of the peripheral blood were found to be genetically similar to the circulating virus in the plasma [19], indicating that they represent the replicating virus population.…”

The Dynamics of HIV-1 Adaptation in Early Infection

“…A recent theoretical analysis of genetic draft argues that it is important in facultatively sexual organisms with large populations (Neher and Shraiman 2011). HIV-1 may be defined as facultatively sexual because recombination between nonidentical genomes depends on the coinfection of cells, which may be rare in peripheral blood (Josefsson et al 2011), but not in other tissues, such as those of the spleen (Jung et al 2002). Neher and Shraiman (2011) argue that with a low recombination rate and pervasive recurrent selection of moderate strength, as may be the case in chronic HIV-1 infection, the stochastic changes in allele frequencies in HIV-1 may be predominantly due to genetic draft.…”

“…Populations were initialized with the haplotype carrying the wild-type allele at each locus. For HIV-1, the rate of recombination between nonidentical genomes depends on the rate of co-infection of cells, which is high in splenocytes (Jung et al 2002), but low in peripheral blood mononuclear cells (Josefsson et al 2011). Because of this, the recombination rate may be as high as r = 10 23 per pair of adjacent nucleotide sites per generation or 1-2 orders of magnitude lower (Levy et al 2004;Shriner et al 2004a;Neher and Leitner 2010;Schlub et al 2010;Batorsky et al 2011).…”

“…For HIV-1, the rate of recombination between nonidentical genomes depends on the rate of co-infection of cells, which may be as high as a mean of three integrated viral genomes (proviruses) per infected splenocyte (Jung et al 2002), or only a single provirus per infected peripheral blood mononuclear cell (Josefsson et al 2011). Therefore, between distantly separated epitopes there may be free to no recombination, depending on the rate of cell co-infection.…”