HIV-1 persistence in the CNS: Mechanisms of latency, pathogenesis and an update on eradication strategies

Sonti, Shilpa; Sharma, Adhikarimayum Lakhikumar; Tyagi, Mudit

doi:10.1016/j.virusres.2021.198523

Cited by 18 publications

(6 citation statements)

References 229 publications

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“…Tat also directly interacts with the histone acetyltransferase p300 and with the closely related CREB-binding protein (CBP) both in vitro and in vivo, and it targets these proteins to the integrated LTR promoter [96,97]. In a recent review, we have outlined the various mechanisms through which viral proteins modulate HIV latency in CNS cells [9]. CNS tissue damage and neuroinflammation in the presence of Tat may lead to the development of HAND [98].…”

Section: Tatmentioning

confidence: 99%

“…Fortunately, new ART regimens are quite efficient in eliminating HIV sanctuaries; however, the latent pool remains invincible. Recent evidence has shown that unintegrated HIV can also produce viral proteins, which exacerbate the host immune response and lead to excessive toxicity and cell death [9]. Hence, to make ART more effective, research efforts have been diverted to identify the mechanisms through which latent HIV can be reactivated before being targeted by antiretrovirals [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Recent evidence has shown that unintegrated HIV can also produce viral proteins, which exacerbate the host immune response and lead to excessive toxicity and cell death [9]. Hence, to make ART more effective, research efforts have been diverted to identify the mechanisms through which latent HIV can be reactivated before being targeted by antiretrovirals [9][10][11][12][13]. Latency reversal agents such as romidepsin, JQ-1, and panobinostat have effectively reactivated the peripheral latent viral reservoir.…”

Section: Introductionmentioning

confidence: 99%

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Crossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir

et al. 2022

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Drug abuse is a common comorbidity in people infected with HIV. HIV-infected individuals who abuse drugs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A modest proportion of HIV-infected individuals develop HIV-associated neurocognitive issues, the severity of which further increases with drug abuse. Moreover, the tendency of the virus to go into latency in certain cellular reservoirs again complicates the elimination of HIV and HIV-associated illnesses. Antiretroviral therapy (ART) successfully decreased the overall viral load in infected people, yet it does not effectively eliminate the virus from all latent reservoirs. Although ART increased the life expectancy of infected individuals, it showed inconsistent improvement in CNS functioning, thus decreasing the quality of life. Research efforts have been dedicated to identifying common mechanisms through which HIV and drug abuse lead to neurotoxicity and CNS dysfunction. Therefore, in order to develop an effective treatment regimen to treat neurocognitive and related symptoms in HIV-infected patients, it is crucial to understand the involved mechanisms of neurotoxicity. Eventually, those mechanisms could lead the way to design and develop novel therapeutic strategies addressing both CNS HIV reservoir and illicit drug use by HIV patients.

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Section: Tatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Crossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir

et al. 2022

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“…The latent HIV provirus, the hallmark of HIV latency, is integrated viral DNA that is transcriptionally silent and cannot be reached by the current combination antiretroviral therapy (cART), thus posing a great obstacle to the treatment and cure of HIV infection [37][38][39][40][41][42][43][44]. Attempts to cure HIV infection in patients undergoing cART require the effective targeting of all possible viral reservoirs in all anatomical sites.…”

Section: Hiv Latency In the Cnsmentioning

confidence: 99%

Human Immunodeficiency Virus Type-1 (HIV-1) Transcriptional Regulation, Latency and Therapy in the Central Nervous System

Hokello

Sharma

Tyagi³

et al. 2021

Vaccines

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The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result of sustained HIV replication in the CNS even in the face of combination antiretroviral therapy, there is a high incidence of HIV-associated neurocognitive disorders (HAND). This article, therefore, provides a comprehensive review of HIV transcriptional regulation, latency, and therapy in the CNS.

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“… 11 , 12 , 13 , 14 These impairments under the influence of illegal drugs are also a potent cofactor that impedes timely diagnosis of HIV transmission, pathogenesis, and adherence to therapy. 13 , 15 Clinical studies implicate drug abuse in increased viral load, accelerated disease progression, and worsening of AIDS-related mortality even in ART-adherent patients. 16 , 17 Therefore, these drugs remain a major obstacle in combating the global HIV epidemic.…”

Section: Introductionmentioning

confidence: 99%