Strategies to target non-T-cell HIV reservoirs

Sacha, Jonah B.; Ndhlovu, Lishomwa C.

doi:10.1097/coh.0000000000000283

Cited by 18 publications

(10 citation statements)

References 56 publications

(57 reference statements)

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“…The current “shock and kill” strategy hinges on the drugs known as latency reversing agents (LRAs) that induce viral production in latently-infected cells [13, 133–135]. Presently, however, latency reversal has been developed to be specific for CD4+ T cell biology, and does not account for the possibility of persistent reservoirs in cells other than T cells [136, 137], reflecting lacunae in our understanding of non-T cell reservoirs [28]. Therefore, a dedicated strategy to eliminate HIV-1 reservoirs requires a better understanding of the role of non-T cell reservoirs using in vivo and ex vivo experimentation.…”

Section: Resultsmentioning

confidence: 99%

Are T cells the only HIV-1 reservoir?

2016

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Current antiretroviral therapies have improved the duration and quality of life of people living with HIV-1. However, viral reservoirs impede complete eradication of the virus. Although there are many strategies to eliminate infectious virus, the most actively pursued are latency reversing agents in conjunction with immune modulation. This strategy, known as “shock and kill”, has been tested primarily against the most widely recognized HIV-1 latent reservoir found in resting memory CD4+ T cells. This is in part because of the dearth of conclusive evidence about the existence of non-T cell reservoirs. Studies of non-T cell reservoirs have been difficult to interpret because of technical and biological issues that have hampered a better understanding. This review considers the current knowledge of non-T cell reservoirs, the challenges encountered in a better understanding of these populations, and their implications for HIV-1 cure research.

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Section: Resultsmentioning

confidence: 99%

Are T cells the only HIV-1 reservoir?

2016

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“…HIV can persist in these viral reservoirs for years with little or no productive infection and can reactivate later 1 . In contrast to initial belief, latent HIV reservoirs are present beyond the realm of memory CD4 + T cells 2 3 4 5 . Subpopulations of all kind of immune cells such as dendritic cells, hematopoietic progenitor cells, natural killer cells, mast cells, monocytes, macrophages, etc.…”

mentioning

confidence: 85%

Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection

Nair

Sagar

Pilakka-Kanthikeel

2016

Sci Rep

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Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.

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“…macrophages, exist as well and these are found in sanctuaries such as the brain [19]. The importance to reduce the pool of all latently-infected reservoirs has been discussed recently [29]. The main challenges one expects to encounter when targeting reservoirs located in a sanctuary such as the brain are [26,134]:…”

Section: The Latency Reversing Agentsmentioning

confidence: 99%

“…Although it is important to eliminate the CD4+ reservoir other cell types harboring HIV should also be targeted. Moreover, there is a great demand for strategies, that facilitate drug penetration into reservoirs located in sanctuaries such as the brain and the lymph nodes [29] Gene therapy is based on gene editing with the recent advance of the CRISPR/Cas9 system being the most attractive technology to target both viral genes and cellular genes such as the CCR5 co-receptor. This system uses a guide RNA coupled to a Cas9 nuclease, which targets specifically the provirus and mediates the excision of the integrated vital genome [30].…”

Section: Introductionmentioning

confidence: 99%

On the way to find a cure: Purging latent HIV-1 reservoirs

Schwartz

Bouchat

Marban

et al. 2017

Biochemical Pharmacology

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Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill). This review focuses mainly on the recent advances made in the "shock and kill" therapy. We believe that a cure or a remission will come from combinatorial approaches i.e. combination of drugs to reactivate the dormant virus from all the reservoirs including the one located in sanctuaries, and combination of strategies boosting the immune system. Alternative strategies based on cell and gene therapy or based in inducing deep latency, which are evoked in this review reinforce the idea that at least a remission is attainable.

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Strategies to target non-T-cell HIV reservoirs

Cited by 18 publications

References 56 publications

Are T cells the only HIV-1 reservoir?

Are T cells the only HIV-1 reservoir?

Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection

On the way to find a cure: Purging latent HIV-1 reservoirs

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