HIV Neurological Disorders: 2nd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 1881

Special Issue Editor


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Guest Editor
Department of Biology, Morgan State University, Baltimore, MD 21251, USA
Interests: neuroscience; neuropathology; cell biology; HIV
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Special Issue Information

Dear Colleagues,

It became apparent from the first Special Issue on HIV neurological disorders (https://www.mdpi.com/journal/viruses/special_issues/HIV_Neurological_Disorders) that there are many unresolved neurologic and psychological challenges associated with HIV that are worthy of discussion. These challenges include, but are not limited to, clinical manifestations, quantitative diagnostic measures, pathological mechanisms and treatment developments. This second Special Issue on HIV Neurological Disorders can address the different challenges clinicians and researchers in the field are now facing.

The mechanisms for the production of HIV-related neurologic disorders remain elusive and complex. In many parts of the world, opportunistic infections still present a continued challenge. Where treatment is available, patients may eventually present with HIV noninfectious comorbidities. Both these situations need to be addressed, but an underlying point in both is the presence of HIV-associated inflammation. In addition, abuse of drugs can complicate treatment and lead to poor outcomes, particularly where the nervous system is concerned. 

Chronic inflammation associated with HIV infection is the main candidate in regard to HIV neurological comorbidities, but there is a need for both clinical and basic science research addressing all aspects of HIV neurologic disorders.

Dr. Frank Denaro
Guest Editor

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Keywords

  • neuroinflammation
  • chronic HIV inflammation
  • HIV reservoir
  • HIV proteins
  • HIV receptors
  • HIV models
  • drugs of abuse
  • AIDS dementia complex
  • HIV noninfectious comorbidities
  • HIV healthcare disparities
  • HIV neuropathology

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Related Special Issue

Published Papers (2 papers)

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Research

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17 pages, 1553 KiB  
Article
Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue
by Marieke M. Nühn, Stephanie B. H. Gumbs, Pauline J. Schipper, Irene Drosou, Lavina Gharu, Ninée V. E. J. Buchholtz, Gijsje J. L. J. Snijders, Frederieke A. J. Gigase, Annemarie M. J. Wensing, Jori Symons, Lot D. de Witte and Monique Nijhuis
Viruses 2025, 17(4), 467; https://doi.org/10.3390/v17040467 - 25 Mar 2025
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Abstract
A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the [...] Read more.
A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b+) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4+ T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4+ T cells, while the remaining viruses replicated only in CD4+ T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies. Full article
(This article belongs to the Special Issue HIV Neurological Disorders: 2nd Edition)
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Review

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26 pages, 1668 KiB  
Review
Neuroinflammation, Blood–Brain Barrier, and HIV Reservoirs in the CNS: An In-Depth Exploration of Latency Mechanisms and Emerging Therapeutic Strategies
by Noor Said and Vishwanath Venketaraman
Viruses 2025, 17(4), 572; https://doi.org/10.3390/v17040572 - 16 Apr 2025
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Abstract
Despite the success of antiretroviral therapy (ART) in suppressing viral replication in the blood, HIV persists in the central nervous system (CNS) and causes chronic neurocognitive impairment, a hallmark of HIV-associated neurocognitive disorders (HAND). This review looks at the complex interactions among HIV, [...] Read more.
Despite the success of antiretroviral therapy (ART) in suppressing viral replication in the blood, HIV persists in the central nervous system (CNS) and causes chronic neurocognitive impairment, a hallmark of HIV-associated neurocognitive disorders (HAND). This review looks at the complex interactions among HIV, the blood–brain barrier (BBB), neuroinflammation, and the roles of viral proteins, immune cell trafficking, and pro-inflammatory mediators in establishing and maintaining latent viral reservoirs in the CNS, particularly microglia and astrocytes. Key findings show disruption of the BBB, monocyte infiltration, and activation of CNS-resident cells by HIV proteins like Tat and gp120, contributing to the neuroinflammatory environment and neuronal damage. Advances in epigenetic regulation of latency have identified targets like histone modifications and DNA methylation, and new therapeutic strategies like latency-reversing agents (LRAs), gene editing (CRISPR/Cas9), and nanoparticle-based drug delivery also offer hope. While we have made significant progress in understanding the molecular basis of HIV persistence in the CNS, overcoming the challenges of BBB penetration and neuroinflammation is key to developing effective therapies. Further research into combination therapies and novel drug delivery systems will help improve outcomes for HAND patients and bring us closer to a functional cure for HIV. Full article
(This article belongs to the Special Issue HIV Neurological Disorders: 2nd Edition)
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