The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents
Joint Authors
Gavegnano, Christina
Kim, Baek
Schinazi, Raymond F.
Kennedy, Edward M.
Source
Molecular Biology International
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-07-01
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Macrophages are ubiquitous and represent a significant viral reservoir for HIV-1.
Macrophages are nondividing, terminally differentiated cells, which have a unique cellular microenvironment relative to actively dividing T lymphocytes, all of which can impact HIV-1 infection/replication, design of inhibitors targeting viral replication in these cells, emergence of mutations within the HIV-1 genome, and disease progression.
Scarce dNTPs drive rNTP incorporation into the proviral DNA in macrophages but not lymphocytes.
Furthermore, the efficacy of a ribose-based inhibitor that potently inhibits HIV-1 replication in macrophages, has prompted a reconsideration of the previously accepted dogma that 2′-deoxy-based inhibitors demonstrate effective inhibition of HIV-1 replication.
Additionally, higher levels of dUTP and rNTP incorporation in macrophages, and lack of repair mechanisms relative to lymphocytes, provide a further mechanistic understanding required to develop targeted inhibition of viral replication in macrophages.
Together, the concentrations of dNTPs and rNTPs within macrophages comprise a distinctive cellular environment that directly impacts HIV-1 replication in macrophages and provides unique insight into novel therapeutic mechanisms that could be exploited to eliminate virus from these cells.
American Psychological Association (APA)
Gavegnano, Christina& Kennedy, Edward M.& Kim, Baek& Schinazi, Raymond F.. 2012. The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents. Molecular Biology International،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-486185
Modern Language Association (MLA)
Gavegnano, Christina…[et al.]. The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents. Molecular Biology International No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-486185
American Medical Association (AMA)
Gavegnano, Christina& Kennedy, Edward M.& Kim, Baek& Schinazi, Raymond F.. The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents. Molecular Biology International. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-486185
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-486185