Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission

Groot, Fedde; Capel, Toni M. van; Schuitemaker, Joost H. N.; Berkhout, Ben; Jong, Esther C. de

doi:10.1186/1742-4690-3-52

Cited by 66 publications

(24 citation statements)

References 64 publications

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“…This observation is consistent with several other studies that have shown initial HIV infection of T EM in diverse settings such as cervico-vaginal tissue, dendritic cell mediated transmission, and a humanized mouse model system (Groot et al, 2006; Nie et al, 2009; Saba et al, 2010). Preferential depletion of the T EM compartment is a characteristic feature of early infection in both human HIV and SIV model systems, particularly in mucosal sites such as the gut associated lymphoid tissue (Brenchley, 2004; Douek et al, 2003; Mehandru, 2004).…”

Section: Discussionsupporting

confidence: 92%

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

et al. 2012

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In utero priming to malaria antigens renders cord blood mononuclear cells (CBMC) more susceptible to productive HIV infection in vitro in the absence of exogenous stimulation. This provides a unique model to better understand mechanisms affecting lymphocyte susceptibility to HIV infection in vivo. Effector memory CD3+CD4+ T cells (TEM) were the exclusive initial targets of HIV with rapid spread to central memory cells. HIV susceptibility correlated with increased expression of CD25 and HLA-DR on TEM. Virus entered all samples equally, however gag/pol RNA was only detected in HIV susceptible samples, suggesting regulation of proviral gene transcription. Targeted analysis of human genes in memory T cells showed greater expression of IFNG, NFATc1, IRF1, FOS, and PPIA and decreased expression YY1 and TFCP2 in HIV susceptible samples. Thus fetal priming to exogenous antigens enhances specific proviral gene transcription pathways in effector memory cells that may increase risk of vertical transmission of HIV.

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Section: Discussionsupporting

confidence: 92%

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

et al. 2012

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“…This observation suggests that R5 and X4 variants are compartmentalized in different host cell types, or alternatively, their recombinants have low fitness and do not grow out in the viral population. Several previous studies have shown that X4 variants preferentially infect naive T cells and that R5 variants preferentially infect memory T cells (52)(53)(54). However, one study observed that the level of integration is lower in resting naive T cells than in memory T cells regardless of the coreceptor tropisms within the viral population (55).…”

Section: Discussionmentioning

confidence: 99%

Deep Sequencing of the HIV-1 env Gene Reveals Discrete X4 Lineages and Linkage Disequilibrium between X4 and R5 Viruses in the V1/V2 and V3 Variable Regions

Zhou

Bednar

Sturdevant

et al. 2016

J Virol

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HIV-1 requires the CD4 receptor and a coreceptor (CCR5 [R5 phenotype] or CXCR4 [X4 phenotype]) to enter cells. Coreceptor tropism can be assessed by either phenotypic or genotypic analysis, the latter using bioinformatics algorithms to predict tropism based on the env V3 sequence. We used the Primer ID sequencing strategy with the MiSeq sequencing platform to reveal the structure of viral populations in the V1/V2 and C2/V3 regions of the HIV-1 env gene in 30 late-stage and 6 early-stage subjects. We also used endpoint dilution PCR followed by cloning of env genes to create pseudotyped virus to explore the link between genotypic predictions and phenotypic assessment of coreceptor usage. We found out that the most stringently sequence-based calls of X4 variants (Geno2Pheno false-positive rate [FPR] of <2%) formed distinct lineages within the viral population, and these were detected in 24 of 30 late-stage samples (80%), which was significantly higher than what has been seen previously by using other approaches. Non-X4 lineages were not skewed toward lower FPR scores in X4-containing populations. Phenotypic assays showed that variants with an intermediate FPR (2 to 20%) could be either X4/dual-tropic or R5 variants, although the X4 variants made up only about 25% of the lineages with an FPR of <10%, and these variants carried a distinctive sequence change. Phylogenetic analysis of both the V1/V2 and C2/V3 regions showed evidence of recombination within but very little recombination between the X4 and R5 lineages, suggesting that these populations are genetically isolated. IMPORTANCEPrimer ID sequencing provides a novel approach to study genetic structures of viral populations. X4 variants may be more prevalent than previously reported when assessed by using next-generation sequencing (NGS) and with a greater depth of sampling than single-genome amplification (SGA). Phylogenetic analysis to identify lineages of sequences with intermediate FPR values may provide additional information for accurately predicting X4 variants by using V3 sequences. Limited recombination occurs between X4 and R5 lineages, suggesting that X4 and R5 variants are genetically isolated and may be replicating in different cell types or that X4/R5 recombinants have reduced fitness. H uman immunodeficiency virus type 1 (HIV-1) requires the CD4 receptor and a coreceptor to infect host cells. Entry is mediated by the viral envelope protein (Env), which is processed to give two associated subunits, gp120 and gp41, that assemble into a trimeric structure embedded in the viral envelope/membrane. The binding of gp120 to CD4 triggers a structural change that exposes its variable region 3 (V3) loop, which is part of the coreceptor domain (1, 2). The majority of transmitted/founder (T/F) viruses and viruses isolated from the clinically latent stage in HIV-infected subjects use CCR5 as the coreceptor, making the virus CCR5 tropic (or an R5 virus). The virus can evolve to use CXCR4 (CXCR4 tropic [or an X4 virus]), and viruses that have switched core...

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“…Importantly, the coreceptor CCR5 is expressed primarily on the T CM , T EM , and T TE subsets, not on "naïve" T cells (22)(23)(24). In contrast, CXCR4 is expressed on both naïve and memory T cell subsets.…”

Section: R5-tropic Viruses Fuse With and Infect Cells Bearing Phenotymentioning

confidence: 99%

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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Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission

Cited by 66 publications

References 64 publications

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

Deep Sequencing of the HIV-1 env Gene Reveals Discrete X4 Lineages and Linkage Disequilibrium between X4 and R5 Viruses in the V1/V2 and V3 Variable Regions

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

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Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission

Cited by 66 publications

References 64 publications

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility

Deep Sequencing of the HIV-1 env Gene Reveals Discrete X4 Lineages and Linkage Disequilibrium between X4 and R5 Viruses in the V1/V2 and V3 Variable Regions

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

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