A Doubly Fluorescent HIV-1 Reporter Shows that the Majority of Integrated HIV-1 Is Latent Shortly after Infection

Dahabieh, Matthew S.; Ooms, Marcel; Simon, Viviana; Sadowski, Ivan

doi:10.1128/jvi.03478-12

Cited by 97 publications

(157 citation statements)

References 53 publications

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“…In contrast to a prevailing model in which latency is thought to arise when activated cells are infected and survive long enough to return to a resting state, our assay directly infects unstimulated CD4 ϩ T cells. Direct infection of resting cells is an alternative model for the generation of latently infected cells, supported by studies demonstrating that HIV can undergo immediate postintegration silencing after the infection of resting CD4 ϩ T cells (43)(44)(45). Latently infected T SCM cells could potentially be generated in either model: either during a period of full or partial activation, as supported by low TREC levels in this subset, or by direct silent infection.…”

Section: Discussionmentioning

confidence: 92%

CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

Tabler

Lucera

Haqqani

et al. 2014

J Virol

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CD4؉ and CD8 ؉ memory T cells with stem cell-like properties (T SCM cells) have been identified in mice, humans, and nonhuman primates and are being investigated for antitumor and antiviral vaccines and immunotherapies. Whether CD4 ؉ T SCM cells are infected by human immunodeficiency virus (HIV) was investigated by using a combination HIV reporter virus system in vitro and by direct staining for HIV p24 antigen ex vivo. A proportion of T SCM cells were found to express the HIV coreceptors CCR5 and CXCR4 and were infected by HIV both in vitro and in vivo. Analysis of viral outcome following fusion using the combination reporter virus system revealed that T SCM cells can become productively or latently infected, although the vast majority of T SCM cells are abortively infected. Knockdown of the HIV restriction factor SAMHD1 using Vpx-containing simian immunodeficiency virus (SIV) virion-like particles enhanced the productive infection of T SCM cells, indicating that SAMHD1 contributes to abortive infection in these cells. These results demonstrate that CD4؉ T SCM cells are targets for HIV infection, that they become productively or latently infected at low levels, and that SAMHD1 expression promotes abortive infection of this important memory cell subset. IMPORTANCE Here we demonstrate the susceptibility of CD4 ؉ memory stem cells (T SCM cells) to infection by HIV in vitro and in vivo, provide an in-depth analysis of coreceptor expression, demonstrate the infection of naïve and memory CD4؉ T cell subsets with both CCR5-and CXCR4-tropic HIV, and also perform outcome analysis to calculate the percentage of cells that are productively, latently, or abortively infected. Through these outcome studies, we determined that the vast majority of T SCM cells are abortively infected by HIV, and we demonstrate that knockdown of SAMHD1 significantly increases the frequency of infection of this CD4 ؉ T cell subset, indicating that SAMHD1 is an active restriction factor in T SCM cells.

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Section: Discussionmentioning

confidence: 92%

CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

Tabler

Lucera

Haqqani

et al. 2014

J Virol

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“…Late reverse transcription (RT) and 2-LTR circle copies determination was performed by TaqMan qPCR as described. 34 …”

Section: Real-time Qpcr Analysismentioning

confidence: 99%

“…34 RGH differentiates between silent latent infection and active infection based on Gag-enhanced green fluorescence protein (eGFP; green) and Nef-mCherry (red) fluorescence: early eGFP indicates active infection, mCherry indicates latent infection, and dual positive of both signals in 1 cell depicts de novo Gag expression and integrated latent virus ( Figure 3A). Using this tool, pseudoviruses with X4-tropic HxB2 (X4-RGH) and R5-tropic JR-FL (R5-RGH) envelopes were generated.…”

Section: Establishment Of Hcmv Latent Infection In Pb-derived Cd34mentioning

confidence: 99%

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

et al. 2017

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“…Although clinical studies have indicated the existence of HIV-1 latency in myeloid cells and ex vivo analysis also indicated the potential of myeloid cells as a latent-HIV-1 reservoir, the establishment of an optimal model of HIV-1 latency reflecting HIV/AIDS patients is required (60)(61)(62). Recently, a latent HIV-1 infection model was established by using isolated CD4 T cells from peripheral blood mononuclear cells (63,64). However, there is no report of a model for the analysis of latent HIV-1 infection in primary myeloid cells.…”

Section: Discussionmentioning

confidence: 99%

COMMD1/Murr1 Reinforces HIV-1 Latent Infection through IκB-α Stabilization

Taura

Kudo

Kariya

et al. 2015

J Virol

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A Doubly Fluorescent HIV-1 Reporter Shows that the Majority of Integrated HIV-1 Is Latent Shortly after Infection

Cited by 97 publications

References 53 publications

CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

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

COMMD1/Murr1 Reinforces HIV-1 Latent Infection through IκB-α Stabilization

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A Doubly Fluorescent HIV-1 Reporter Shows that the Majority of Integrated HIV-1 Is Latent Shortly after Infection

Cited by 97 publications

References 53 publications

CD4 + Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

CD4 + Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

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

COMMD1/Murr1 Reinforces HIV-1 Latent Infection through IκB-α Stabilization

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CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression

CD4 ⁺ Memory Stem Cells Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression