HIV-1 persistence in CD4+ T cells with stem cell–like properties

Abstract

Cellular HIV-1 reservoirs that persist despite antiretroviral treatment are incompletely defined. We show that during suppressive antiretroviral therapy, CD4+ T memory stem cells (TSCM) harbor high per-cell levels of HIV-1 DNA, and make increasing contributions to the total viral CD4+ T cell reservoir over time. Moreover, phylogenetic studies suggested long-term persistence of viral quasispecies in CD4+ TSCM cells. Thus, HIV-1 may exploit stem cell characteristics of cellular immune memory to promote long-term viral persistence.

Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1

“…The presence of reservoir compartments with different levels of LRA penetration does not alter our results, as they are stated in terms of total reservoir reduction. If, however, these compartments vary in activation or death rates (41), or if dynamics of activated cells depends on their source compartment, then our model may need to be modified. Moreover, if spatial population structure affects viral replication, viral dynamics above the detection limit (from which we estimated parameters r and A) may not correspond straightforwardly to the infection/death rates in early infection, due to local limitations in target cell density (42).…”

Latent human cytomegalovirus enhances HIV-1 infection in CD34+ progenitor cells

“…One of the largest hurdles to cure HIV-1 is the clearance of latent reservoirs that exist in different cell types and in different tissue compartments. Apart from memory CD4 1 T cells, 51 several studies have proposed that CD34 hematopoietic progenitor cells could be another HIV-1 latent reservoir. 9,10,52 Although still controversial, the presence of HIV-1 restriction factors and innate immune response could affect the efficiency of HIV-1 infection into these cells.…”

“…Our data show that latent HCMV can downregulate HIV restriction factors ( Figure 6) and upregulate CXCR4 and CCR5 ( Figure 5A,C). 47 HCMV has also been shown to suppress type I IFN responses during productive infection, 51 but whether it occurs during latent infection in PB-CD34 cells remains to be investigated. If so, this would also affect interferon-induced innate sensors IFI16, cGAS, and RIG-I as well as restriction factors that would potentially affect HIV-1 infection and replication.…”

T memory stem cells are the hierarchical apex of adult T-cell leukemia

“…31 Moreover, the identification of the T SCM population with stem cell-like features 12,13 has produced the new concept that the T SCM population is a reservoir of another retrovirus, HIV-1. 32 Based on these findings, we investigated the phenotypic architecture and the distribution of genetic marks including HTLV-1 DNA, a definite first hit for ATL, and ATL clone-specific provirus integration sites, in CD4 These findings should be validated using in vivo xenograft models, 4,34 however, it should be heeded that HTLV-1-infected cells rather than ATL clones could generate xenografts. In fact, although a number of xenograft models of ATL have been reported, [35][36][37][38] identical ATL clones engrafted in only a few cases.…”