Combinatorial Use of Both Epigenetic and Non-Epigenetic Mechanisms to Efficiently Reactivate HIV Latency

Hokello, Joseph; Sharma, Adhikarimayum Lakhikumar; Tyagi, Mudit

doi:10.3390/ijms22073697

Cited by 6 publications

(3 citation statements)

References 91 publications

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“…The resultant complex formed is made up of multiple proteins comprising TBP and TAF, referred to as TFIID, which, along with three SP1 binding sites, constitutes the minimal transcription complex that can induce basal HIV LTR promoter transcription. However, for efficient HIV LTR promoter-mediated transcription, it requires the TFIID interaction with upstream enhancer binding factors such as NF-κB, AP-1 or NFAT [75,[82][83][84][85][86][87][88][89][90]. Transcription factor II H (TFIIH) exhibits kinase activity (CDK7) required for promoter clearance by phosphorylating the C-terminal domain (CTD) of RNAP II, whose recruitment to the HIV LTR promoter is reported to be the major determinant in HIV transcription, especially HIV-1 transcription initiation [80,91,92].…”

Section: Transcriptionmentioning

confidence: 99%

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

Hokello,

Tyagi,

Owor

et al. 2024

Life

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The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. This review provides new insights into the molecular biology of HIV, wherein the HIV life cycle is discussed in detail. Insights into the possible mechanism for the Th1 to Th2 shift during HIV infection and the preferential infection of Th2 cells during the late symptomatic stage of HIV disease are also discussed.

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Section: Transcriptionmentioning

confidence: 99%

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

Hokello,

Tyagi,

Owor

et al. 2024

Life

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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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“…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%

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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Combinatorial Use of Both Epigenetic and Non-Epigenetic Mechanisms to Efficiently Reactivate HIV Latency

Cited by 6 publications

References 91 publications

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

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

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

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