HIV Latency in Myeloid Cells: Challenges for a Cure

Chitrakar, Alisha; Sanz, Marta González; Maggirwar, Sanjay B.; Soriano-Sarabia, Natalia

doi:10.3390/pathogens11060611

Cited by 16 publications

(9 citation statements)

References 244 publications

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“…However, additional investigations seeking to elucidate the specific role of macrophages in HIV-1 transmission, particularly in mucosal tissues, are needed to shed light on the early events that contribute to the establishment of an infection. Finally, infected macrophages are not susceptible to the virus-induced cytopathic effect, and can thus participate, together with latently infected CD4+ T cells, in the early establishment and persistence of virus reservoirs in numerous host tissues (for recent reviews, see [ 2 , 10 ]). As recently shown [ 3 ], these virus reservoirs in myeloid cells can be detected over several years in patients on cART.…”

Section: Macrophages As Cellular Targets Of Hiv-1 In Vivomentioning

confidence: 99%

“…Intriguingly, it was suggested that gut macrophages are resistant to HIV-1 infection (for reviews, see [ 2 , 49 ]), even though it was reported that duodenal macrophages from gut biopsies of ART-suppressed people living with HIV can express viral antigens [ 50 ]. In vitro, it has been shown that intestinal macrophages are less permissive than cervicovaginal macrophages to HIV-1 infection and replication [ 51 ].…”

Section: Macrophages As Cellular Targets Of Hiv-1 In Vivomentioning

confidence: 99%

“…Initially described, together with conventional dendritic cells (DCs) and monocytes, as cells of the mononuclear phagocyte system derived from a common myeloid progenitor, macrophages are found in almost all tissues of the body where they play several critical roles in tissue homeostasis, both in physiological and pathological conditions (for review, see [ 1 ]). While the role of non-differentiated blood monocytes as HIV-1 target cells was previously debated [ 2 ], it was recently reported that latent HIV-1 could be detected in monocytes in half of people living with HIV receiving effective combined antiretroviral therapy (cART) [ 3 ]. In contrast, terminally differentiated DCs and tissue macrophages were rapidly recognized, in addition to CD4+ T lymphocytes, as productively infected target cells of HIV-1 (for reviews, see [ 4 , 5 , 6 , 7 ]).…”

Section: Introductionmentioning

confidence: 99%

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Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Woottum,

Yan,

Sayettat

et al. 2024

Viruses

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Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

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Section: Macrophages As Cellular Targets Of Hiv-1 In Vivomentioning

confidence: 99%

Section: Macrophages As Cellular Targets Of Hiv-1 In Vivomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Woottum,

Yan,

Sayettat

et al. 2024

Viruses

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“…Additionally, while CD4+ T cells represent the main reservoir of latently infected cells, monocytes and macrophages are becoming increasingly recognized as additional sources of latent viral reservoirs. 5 This review focuses primarily on the roles of RNA molecules in HIV regulation of HIV latency in CD4+ T cells and lymphocytic cell lines; however, observations of their roles in monocytes, macrophages, and promonocytic cell lines are also discussed.…”

Section: Introductionmentioning

confidence: 99%

An Evaluation on the Role of Non-Coding RNA in HIV Transcription and Latency: A Review

Ramirez¹,

Pantoja²,

Beliakova-Bethell³

2023

HIV

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The existence of latent cellular reservoirs is recognized as the major barrier to an HIV cure. Reactivating and eliminating "shock and kill" or permanently silencing "block and lock" the latent HIV reservoir, as well as gene editing, remain promising approaches, but so far have proven to be only partially successful. Moreover, using latency reversing agents or "block and lock" drugs pose additional considerations, including the ability to cause cellular toxicity, a potential lack of specificity for HIV, or low potency when each agent is used alone. RNA molecules, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are becoming increasingly recognized as important regulators of gene expression. RNA-based approaches for combatting HIV latency represent a promising strategy since both miRNAs and lncRNAs are more cell-type and tissue specific than protein coding genes. Thus, a higher specificity of targeting the latent HIV reservoir with less overall cellular toxicity can likely be achieved. In this review, we summarize current knowledge about HIV gene expression regulation by miRNAs and lncRNAs encoded in the human genome, as well as regulatory molecules encoded in the HIV genome. We discuss both the transcriptional and post-transcriptional regulation of HIV gene expression to align with the current definition of latency, and describe RNA molecules that either promote HIV latency or have antilatency properties. Finally, we provide perspectives on using each class of RNAs as potential targets for combatting HIV latency, and describe the complexity of the interactions between different RNA molecules, their protein targets, and HIV.

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“…HIV-infected monocytes could provide an important mechanism to disseminate the virus to sites, like the central nervous system (CNS) and male genital system, where evidences for compartmentalization of viral populations had been identified. [ 5 ] One possibility is that monocytes are being infected by macrophage-tropic viruses replicating in tissue macrophage. [ 6 ] Defining genetic determinants of viruses in monocytes could enhance our overall understanding of macrophage-tropic viruses in different anatomic sites and have implications for the design of curative strategies for HIV.…”

mentioning

confidence: 99%