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Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review
Journal article   Open access

Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review

Bryan Irish, Zafar Khan, Pooja Jain, Michael Nonnemacher, Vanessa Pirrone, Saifur Rahman, Nirmala Rajagopalan, Joyce Suchitra, Kate Mostoller and Brian Wigdahl
American journal of infectious diseases, v 5(3), pp 231-258
01 Jan 2009
DOI: https://doi.org/10.3844/ajidsp.2009.231.258
PMID: 20352020
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.3844/ajidsp.2009.231.258View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Infectious Diseases Life Sciences & Biomedicine Science & Technology
Problem statement: Infection with retroviruses such as human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1) have been shown to lead to neurodegenerative diseases such as HIV-associated dementia (HAD) or neuroAIDS and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), respectively. Approach: HIV-1-induced neurologic disease is associated with an influx of HIV-infected monocytic cells across the blood-brain barrier. Following neuroinvasion, HIV-1 and viral proteins, in addition to cellular mediators released from infected and uninfected cells participate in astrocytic and neuronal dysregulation, leading to mild to severe neurocognitive disorders. Results: The molecular architecture of viral regulatory components including the Long Terminal Repeat (LTR), genes encoding the viral proteins Tat, Vpr and Nef as well as the envelope gene encoding gp120 and gp41 have been implicated in 'indirect' mechanisms of neuronal injury, mechanisms which are likely responsible for the majority of CNS damage induced by HIV-1 infection. The neuropathogenesis of HAM/TSP is linked, in part, with both intra-and extracellular effectors functions of the viral transactivator protein Tax and likely other viral proteins. Tax is traditionally known to localize in the nucleus of infected cells serving as a regulator of both viral and cellular gene expression. Conclusion/Recommendations: However, recent evidence has suggested that Tax may also accumulate in the cytoplasm and be released from the infected cell through regulated cellular secretion processes. Once in the extracellular environment, Tax may cause functional alterations in cells of the peripheral blood, lymphoid organs and the central nervous system. These extracellular biological activities of Tax are likely very relevant to the neuropathogenesis of HTLV-1 and represent attractive targets for therapeutic intervention.

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Web of Science research areas
Infectious Diseases
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