The CD16+ Monocyte Subset Is More Permissive to Infection and Preferentially Harbors HIV-1 In Vivo

Ellery, Philip; Tippett, Emma; Chiu, Ya‐Lin; Paukovics, Geza; Cameron, Paul; Solomon, Ajantha; Lewin, Sharon R.; Gorry, Paul R; Jaworowski, Anthony; Greene, Warner C.; Sonza, Secondo; Crowe, Suzanne

doi:10.4049/jimmunol.178.10.6581

Cited by 302 publications

(300 citation statements)

References 75 publications

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“…The role these cells play in patients on suppressive cART is not fully understood (43)(44)(45). We sorted myeloid cells from both peripheral blood and GALT from all of the eight patients and found HIV-1 DNA in myeloid cells from peripheral blood and GALT in three and four of the eight patient samples, respectively.…”

Section: Discussionmentioning

confidence: 99%

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

Josefsson

Stockenström

Faria

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

250

296

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Significance Identifying the source and dynamics of persistent HIV-1 during combinational antiretroviral therapy (cART) is crucial for understanding the barriers to curing HIV infection. Through genetic characterization of HIV-1 DNA in infected cells from peripheral blood and gut-associated lymphoid tissue from patients after long-term suppressive cART, our study reveals that the primary barrier to a cure is a remarkably stable pool of infected memory CD4 + T cells. Through in-depth phylogenetic analyses, we determined that the HIV-1 reservoir in these cells from eight patients is kept stable during long-term cART and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes.

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Section: Discussionmentioning

confidence: 99%

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

Josefsson

Stockenström

Faria

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

250

296

View full text Add to dashboard Cite

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“…This is consistent with recent observations that not all macrophage subsets efficiently support HIV transcription. For example, CD16 ϩ monocytes were shown to be more permissive for HIV-1 infection and replication than CD14 ϩ CD16 Ϫ monocytic cells (63,64). We would predict that some tissue resident macrophage populations are infected but do not readily support replication, possibly as a result of negative cellular signals, from receptors such as RON.…”

Section: Discussionmentioning

confidence: 99%

The Receptor Tyrosine Kinase RON Represses HIV-1 Transcription by Targeting RNA Polymerase II Processivity

Klatt

Zhang

Hankey

et al. 2008

The Journal of Immunology

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Efficient HIV-1 transcription requires the induction of cellular transcription factors, such as NF-κB, and the viral factor Tat, which through the recruitment of P-TEFb enhances processive transcription. However, whether cellular signals repress HIV-1 transcription to establish proviral latency has not been well studied. Previously, it has been shown that the receptor tyrosine kinase RON inhibits HIV transcription. To gain insights into the biochemical mechanisms by which RON inhibits transcription we examined the binding of transcription factors to the HIV provirus long terminal repeat using chromatin immunoprecipitation. RON expression decreased basal levels of NF-κB and RNA polymerase II (Pol II) binding to the HIV provirus long terminal repeat but did not prevent the induction of these complexes following treatment with cytokines. However, RON did decrease efficient transcription elongation because reduced RNA Pol II was associated with HIV-1 genomic sequences downstream of the transcriptional start site. There was a correlation between RON expression and increased binding of factors that negatively regulate transcription elongation, NELF, Spt5, and Pcf11. Furthermore, the ability of RON to inhibit HIV-1 transcription was sensitive to a histone deacetylase inhibitor and was associated with nucleosome remodeling. These results indicate that RON represses HIV transcription at multiple transcriptional check points including initiation, elongation and chromatin organization and are the first studies to show that cellular signaling pathways target Pol II pausing to repress gene expression.

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“…Monocytes, monocyte-derived macrophages (MDMs), and tissue macrophages can be productively infected by HIV (2,3). Persistently infected monocytic cells serve as a major reservoir of HIV in lymphoid tissues at all stages of disease and represent a key challenge to eradicating HIV infection.…”

mentioning

confidence: 99%

CpG Protects Human Monocytic Cells against HIV-Vpr–Induced Apoptosis by Cellular Inhibitor of Apoptosis-2 through the Calcium-Activated JNK Pathway in a TLR9-Independent Manner

Saxena

Busca

Pandey

et al. 2011

The Journal of Immunology

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Monocytic cells survive HIV replication and consequent cytopathic effects because of their decreased sensitivity to HIV-induced apoptosis. However, the mechanism underlying this resistance to apoptosis remains poorly understood. Lymphocytic cells are exposed to microbial products because of their translocation from the gut in persons with chronic HIV infections or following coinfections. We hypothesized that activation of monocytic cells by such microbial products through interaction with corresponding TLRs may confer antiapoptotic signals. Using HIV-viral protein R (Vpr)(52–96) peptide as a model apoptosis-inducing agent, we demonstrated that unlike monocyte-derived macrophages, undifferentiated primary human monocytes and promonocytic THP-1 cells are highly susceptible to Vpr(52–96)-induced apoptosis. Interestingly, monocytes and THP-1 cells stimulated with TLR9 agonist CpG induced almost complete resistance to Vpr(52–96)-induced apoptosis, albeit through a TLR9-independent signaling pathway. Moreover, CpG selectively induced the antiapoptotic cellular inhibitor of apoptosis (c-IAP)-2 protein and inhibition of the c-IAP-2 gene by either specific small interfering RNA or synthetic second mitochondrial activator of caspases mimetic reversed CpG-induced resistance against Vpr(52–96)-mediated apoptosis. We demonstrated that c-IAP-2 is regulated by the JNK and calcium signaling pathway, in particular calmodulin-dependent protein kinase-II. Furthermore, inhibition of JNK and the calcium signaling including the calmodulin-dependent protein kinase-II by either pharmacological inhibitors or their specific small interfering RNAs reversed CpG-induced protection against Vpr(52–96)-mediated apoptosis. We also show that CpG induced JNK phosphorylation through activation of the calcium signaling pathway. Taken together, our results suggest that CpG-induced protection may be mediated by c-IAP-2 through the calcium-activated JNK pathway via what appeared to be TLR9-independent signaling pathways.

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The CD16+ Monocyte Subset Is More Permissive to Infection and Preferentially Harbors HIV-1 In Vivo

Cited by 302 publications

References 75 publications

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

The Receptor Tyrosine Kinase RON Represses HIV-1 Transcription by Targeting RNA Polymerase II Processivity

CpG Protects Human Monocytic Cells against HIV-Vpr–Induced Apoptosis by Cellular Inhibitor of Apoptosis-2 through the Calcium-Activated JNK Pathway in a TLR9-Independent Manner

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