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Latent HIV-1 infection occurs in multiple subsets of hematopoietic progenitor cells and is reversed by NF-κB activation.

Abstract：

:The ability of HIV-1 to establish a latent infection presents a barrier to curing HIV. The best-studied reservoir of latent virus in vivo is resting memory CD4(+) T cells, but it has recently been shown that CD34(+) hematopoietic progenitor cells (HPCs) can also become latently infected by HIV-1 in vitro and in vivo. CD34(+) cells are not homogenous, however, and it is not yet known which types of CD34(+) cells support a latent infection. Furthermore, the mechanisms through which latency is established in this cell type are not yet known. Here we report the development of a primary cell model for latent HIV-1 infection in HPCs. We demonstrate that in this model, latent infection can be established in all subsets of HPCs examined, including HPCs with cell surface markers consistent with immature hematopoietic stem and progenitor cells. We further show that the establishment of latent infection in these cells can be reversed by tumor necrosis factor alpha (TNF-α) through an NF-κB-dependent mechanism. In contrast, we do not find evidence for a role of positive transcription elongation factor b (P-TEFb) in the establishment of latent infection in HPCs. Finally, we demonstrate that prostratin and suberoylanilide hydroxamic acid (SAHA), but not hexamethylene bisacetamide (HMBA) or 5-aza-2'-deoxycytidine (Aza-CdR), reactivate latent HIV-1 in HPCs. These findings illuminate the mechanisms through which latent infection can be established in HPCs and suggest common pathways through which latent virus could be reactivated in both HPCs and resting memory T cells to eliminate latent reservoirs of HIV-1.

journal_name

J Virol

journal_title

Journal of virology

authors

McNamara LA,Ganesh JA,Collins KL

doi

10.1128/JVI.00895-12

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

9337-50

issue

17

eissn

0022-538X

issn

1098-5514

pii

JVI.00895-12

journal_volume

86

pub_type

杂志文章

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