HIV-1 Latency and Viral Reservoirs: Existing Reversal Approaches and Potential Technologies, Targets, and Pathways Involved in HIV Latency Studies

Khanal, Sushant; Schank, Madison; Gazzar, Mohamed El; Moorman, Jonathan P.; Yao, Zhi Q.

doi:10.3390/cells10020475

Cited by 32 publications

(49 citation statements)

References 208 publications

(292 reference statements)

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“…This suggests that the signaling pathway would be related to the transcription of the virus ( 63 ). Also, the interaction between the activation of the glycoprotein and the CD4+ T cells activates the PI3K pathway responsible for regulating the migration of T cells and promoting the entry of viral particles after HIV-1 infection ( 64 ). Furthermore, ERK phosphorylation is needed for reverse transcription, regulating virus infectivity ( 65 , 66 ).…”

Section: Spread Of Virus In the Immune Systemmentioning

confidence: 99%

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

Espinar-Buitrago

Muñoz‐Fernández

2022

Front. Immunol.

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Due to the success of combined antiretroviral therapy (cART) in recent years, the pathological outcome of Human Immunodeficiency Virus type 1 (HIV-1) infection has improved substantially, achieving undetectable viral loads in most cases. Nevertheless, the presence of a viral reservoir formed by latently infected cells results in patients having to maintain treatment for life. In the absence of effective eradication strategies against HIV-1, research efforts are focused on obtaining a cure. One of these approaches is the creation of therapeutic vaccines. In this sense, the most promising one up to now is based on the establishing of the immunological synapse between dendritic cells (DCs) and T lymphocytes (TL). DCs are one of the first cells of the immune system to encounter HIV-1 by acting as antigen presenting cells, bringing about the interaction between innate and adaptive immune responses mediated by TL. Furthermore, TL are the end effector, and their response capacity is essential in the adaptive elimination of cells infected by pathogens. In this review, we summarize the knowledge of the interaction between DCs with TL, as well as the characterization of the specific T-cell response against HIV-1 infection. The use of nanotechnology in the design and improvement of vaccines based on DCs has been researched and presented here with a special emphasis.

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Section: Spread Of Virus In the Immune Systemmentioning

confidence: 99%

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

Espinar-Buitrago

Muñoz‐Fernández

2022

Front. Immunol.

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“…Given the fact that individuals on cART maintain high HIV protein viral loads in the CNS throughout their lifetime, HIV proteins are potential causes for the degeneration and amyloid pathology seen in HAND neurons. The HIV Tat protein is one such protein that persists in the CNS despite cART therapy [ 147 ].…”

Section: Role Of Different Cns Cell Types In Alzheimer’s-like Pathologymentioning

confidence: 99%

Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders

et al. 2021

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Despite the widespread success of combined antiretroviral therapy (cART) in suppressing viremia, the prevalence of human immunodeficiency virus (HIV)-associated neurological disorders (HAND) and associated comorbidities such as Alzheimer’s disease (AD)-like symptomatology is higher among people living with HIV. The pathophysiology of observed deficits in HAND is well understood. However, it has been suggested that it is exacerbated by aging. Epidemiological studies have suggested comparable concentrations of the toxic amyloid protein, amyloid-β42 (Aβ42), in the cerebrospinal fluid (CSF) of HAND patients and in the brains of patients with dementia of the Alzheimer’s type. Apart from abnormal amyloid-β (Aβ) metabolism in AD, a better understanding of the role of similar pathophysiologic processes in HAND could be of substantial value. The pathogenesis of HAND involves either the direct effects of the virus or the effect of viral proteins, such as Tat, Gp120, or Nef, as well as the effects of antiretrovirals on amyloid metabolism and tauopathy, leading, in turn, to synaptodendritic alterations and neuroinflammatory milieu in the brain. Additionally, there is a lack of knowledge regarding the causative or bystander role of Alzheimer’s-like pathology in HAND, which is a barrier to the development of therapeutics for HAND. This review attempts to highlight the cause–effect relationship of Alzheimer’s-like pathology with HAND, attempting to dissect the role of HIV-1, HIV viral proteins, and antiretrovirals in patient samples, animal models, and cell culture model systems. Biomarkers associated with Alzheimer’s-like pathology can serve as a tool to assess the neuronal injury in the brain and the associated cognitive deficits. Understanding the factors contributing to the AD-like pathology associated with HAND could set the stage for the future development of therapeutics aimed at abrogating the disease process.

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“…HIV infects multiple cell types including T-cells, monocytes, and macrophages. This complicates eradication strategies as the latent reservoir comprises these multiple cell types [15][16][17][18]. Here, regulation and dynamics of viral gene expression may vary on a cell type basis [19].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types

Blanco

Mahajan

Coronado

et al. 2021

Viruses

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Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects of latency reversal agents (LRAs) in an HIV-infected THP-1 monocyte cell line in vitro. We demonstrate that leading drug treatments synergize activation of the HIV long terminal repeat (LTR) promoter. We establish a latency model in THP-1 monocytes using a replication incompetent HIV reporter vector with functional Tat, and show that chromatin modifiers synergize with a potent transcriptional activator to enhance HIV reactivation, similar to T-cells. Furthermore, leading reactivation cocktails are shown to differentially affect latency reactivation and surface expression of chemokine receptor type 4 (CXCR4), leading to altered host cell migration. This study investigates the effect of chromatin-modifying LRA treatments on HIV latent reactivation and cell migration in monocytes. As previously reported in T-cells, epigenetic mechanisms in monocytes contribute to controlling the relationship between latent reactivation and cell migration. Ultimately, advanced “Shock and Kill” therapy needs to successfully target and account for all host cell types represented in a complex and composite latency milieu.

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HIV-1 Latency and Viral Reservoirs: Existing Reversal Approaches and Potential Technologies, Targets, and Pathways Involved in HIV Latency Studies

Cited by 32 publications

References 208 publications

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

Alzheimer’s-Like Pathology at the Crossroads of HIV-Associated Neurological Disorders

Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types

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