Peering into the HIV reservoir

García, Marcial; Buzón, María J.; Benito, José M.; Rallón, Norma

doi:10.1002/rmv.1981

Cited by 25 publications

(20 citation statements)

References 207 publications

(268 reference statements)

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“…Moreover, with ultrasensitive methods, we can still notice a residual viremia in patients under cART (Dornadula et al, 1999; Bouchat et al, 2016). The main reservoirs are the resting CD4+ T cells but we have now enough evidence which argues for the existence of many other cell reservoirs such as hematopoietic stem cells, dendritic cells, microglial cells and cells from the monocyte-macrophage lineage (reviewed in Marcello, 2006; García et al, 2018; Sung and Margolis, 2018). In addition, some of these reservoirs are found in sanctuaries such as the genital tract, the adipose tissue, the bone marrow and the brain.…”

Section: Introductionmentioning

confidence: 99%

Microglial Cells: The Main HIV-1 Reservoir in the Brain

Wallet

Rovere

Assche

et al. 2019

Front. Cell. Infect. Microbiol.

285

252

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Despite efficient combination of the antiretroviral therapy (cART), which significantly decreased mortality and morbidity of HIV-1 infection, a definitive HIV cure has not been achieved. Hidden HIV-1 in cellular and anatomic reservoirs is the major hurdle toward a functional cure. Microglial cells, the Central Nervous system (CNS) resident macrophages, are one of the major cellular reservoirs of latent HIV-1. These cells are believed to be involved in the emergence of drugs resistance and reseeding peripheral tissues. Moreover, these long-life reservoirs are also involved in the development of HIV-1-associated neurocognitive diseases (HAND). Clearing these infected cells from the brain is therefore crucial to achieve a cure. However, many characteristics of microglial cells and the CNS hinder the eradication of these brain reservoirs. Better understandings of the specific molecular mechanisms of HIV-1 latency in microglial cells should help to design new molecules and new strategies preventing HAND and achieving HIV cure. Moreover, new strategies are needed to circumvent the limitations associated to anatomical sanctuaries with barriers such as the blood brain barrier (BBB) that reduce the access of drugs.

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Section: Introductionmentioning

confidence: 99%

Microglial Cells: The Main HIV-1 Reservoir in the Brain

Wallet

Rovere

Assche

et al. 2019

Front. Cell. Infect. Microbiol.

285

252

View full text Add to dashboard Cite

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“…These reservoirs allow persistence of replication-competent HIV-1 for prolonged periods of time in patients on optimal cART regimens (128). The main HIV cellular reservoir is composed of resting CD4 + T-cells (129), and unfortunately, replication-competent provirus from latent reservoirs is capable of reigniting infection, if therapy is interrupted (130). Peripheral Vg9Vd2 T cells are a novel reservoir of latent HIV-1 infection (131).…”

Section: Platelets During Hiv-1 Treatmentmentioning

confidence: 99%

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

Pretorius

2021

Front. Immunol.

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The immune and inflammatory responses of platelets to human immunodeficiency virus 1 (HIV-1) and its envelope proteins are of great significance to both the treatment of the infection, and to the comorbidities related to systemic inflammation. Platelets can interact with the HIV-1 virus itself, or with viral membrane proteins, or with dysregulated inflammatory molecules in circulation, ensuing from HIV-1 infection. Platelets can facilitate the inhibition of HIV-1 infection via endogenously-produced inhibitors of HIV-1 replication, or the virus can temporarily hide from the immune system inside platelets, whereby platelets act as HIV-1 reservoirs. Platelets are therefore both guardians of the host defence system, and transient reservoirs of the virus. Such reservoirs may be of particular significance during combination antiretroviral therapy (cART) interruption, as it may drive viral persistence, and result in significant implications for treatment. Both HIV-1 envelope proteins and circulating inflammatory molecules can also initiate platelet complex formation with immune cells and erythrocytes. Complex formation cause platelet hypercoagulation and may lead to an increased thrombotic risk. Ultimately, HIV-1 infection can initiate platelet depletion and thrombocytopenia. Because of their relatively short lifespan, platelets are important signalling entities, and could be targeted more directly during HIV-1 infection and cART.

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“…The relative failure of cART to reach a cure is due to the long-term persistence of stable HIV-1-infected cellular reservoirs through several mechanisms including (a) clonal expansion of HIV-1-infected cells due to viral integration in or near genes associated with cell growth, homeostatic proliferation, and antigen-driven proliferation; (b) maintenance of an active reservoir where ongoing HIV-1 replication is observed; (c) antigen stimulation of infected cells; and (d) repression of HIV-1 transcription in latently infected cells (8). This last mechanism of HIV-1 persistence has been extensively studied and corresponds to latently infected cells in which proviruses are stably integrated but produce no or very little RNA or protein due to transcriptional, post-transcriptional, and translational blocks (8)(9)(10). These cells are insensitive to cART and can evade the patient immune system.…”

Section: Introductionmentioning

confidence: 99%

The Current Status of Latency Reversing Agents for HIV-1 Remission

Rodari

Darcis²,

Lint

2021

Annu. Rev. Virol.

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Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due to the persistence of stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed of CD4+ T cells harboring replication-competent latent proviruses. A broadly explored approach to reduce the HIV-1 reservoir size, the shock and kill strategy, consists of reactivating HIV-1 gene expression from the latently infected cellular reservoirs (the shock), followed by killing of the virus-producing infected cells (the kill). Based on improved understanding of the multiple molecular mechanisms controlling HIV-1 latency, distinct classes of latency reversing agents (LRAs) have been studied for their efficiency to reactivate viral gene expression in in vitro and ex vivo cell models. Here, we provide an up-to-date review of these different mechanistic classes of LRAs and discuss optimizations of the shock strategy by combining several LRAs simultaneously or sequentially.

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Peering into the HIV reservoir

Cited by 25 publications

References 207 publications

Microglial Cells: The Main HIV-1 Reservoir in the Brain

Microglial Cells: The Main HIV-1 Reservoir in the Brain

Platelets in HIV: A Guardian of Host Defence or Transient Reservoir of the Virus?

The Current Status of Latency Reversing Agents for HIV-1 Remission

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