HIV-1 transcription in the central nervous system and implications for HIV cure research

Churchill, M, Cowley, D, Wesselingh, S, Gorry, P and Gray, L 2015, 'HIV-1 transcription in the central nervous system and implications for HIV cure research', Journal of NeuroVirology, vol. 21, pp. 290-300.

Document type: Journal Article
Collection: Journal Articles

Title HIV-1 transcription in the central nervous system and implications for HIV cure research
Author(s) Churchill, M
Cowley, D
Wesselingh, S
Gorry, P
Gray, L
Year 2015
Journal name Journal of NeuroVirology
Volume number 21
Start page 290
End page 300
Total pages 11
Publisher Springer
Abstract Human immunodeficiency virus type-1 (HIV-1) invades the central nervous system (CNS) during acute infection which can result in HIV-associated neurocognitive disorders in up to 50 % of patients, even in the presence of combination antiretroviral therapy (cART). Within the CNS, productive HIV-1 infection occurs in the perivascular macrophages and microglia. Astrocytes also become infected, although their infection is restricted and does not give rise to new viral particles. The major barrier to the elimination of HIV-1 is the establishment of viral reservoirs in different anatomical sites throughout the body and viral persistence during long-term treatment with cART. While the predominant viral reservoir is believed to be resting CD4+ T cells in the blood, other anatomical compartments including the CNS, gut-associated lymphoid tissue, bone marrow, and genital tract can also harbour persistently infected cellular reservoirs of HIV-1. Viral latency is predominantly responsible for HIV-1 persistence and is most likely governed at the transcriptional level. Current clinical trials are testing transcriptional activators, in the background of cART, in an attempt to purge these viral reservoirs and reverse viral latency. These strategies aim to activate viral transcription in cells constituting the viral reservoir, so they can be recognised and cleared by the immune system, while new rounds of infection are blocked by co-administration of cART. The CNS has several unique characteristics that may result in differences in viral transcription and in the way latency is established. These include CNS-specific cell types, different transcription factors, altered immune surveillance, and reduced antiretroviral drug bioavailability. A comprehensive understanding of viral transcription and latency in the CNS is required in order to determine treatment outcomes when using transcriptional activators within the CNS.
Subject Medical Virology
Keyword(s) HIV-1
DOI - identifier 10.1007/s13365-014-0271-5
Copyright notice © Journal of NeuroVirology, Inc. 2014
ISSN 1355-0284
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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