Journal article
HIV-1 Latency and Eradication: Past, Present and Future
Current HIV research, v 14(5), pp 431-441
01 Jan 2016
PMID: 27009094
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: It is well established that antiretroviral therapy (ART), while highly effective in controlling HIV replication, cannot eliminate virus from the body. Therefore, the majority of HIV-1-infected individuals remain at risk for developing AIDS due to persistence of infected reservoir cells serving as a source of virus re-emergence. Several reservoirs containing replication competent HIV-1 have been identified, most notably CD4+ T cells. Cells of the myeloid lineage, which are the first line of defense against pathogens and participate in HIV dissemination into sanctuary organs, also serve as cellular reservoirs of HIV-1. In latently infected resting CD4+ T cells, the integrated copies of proviral DNA remain in a dormant state, yet possess the ability to produce replication competent virus after cellular activation. Studies have demonstrated that modification of chromatin structure plays a role in establishing persistence, in part suggesting that latency is, controlled epigenetically.
Conclusion: Current efforts to eradicate HIV-1 from this cell population focus primarily on a "shock and kill" approach through cellular reactivation to trigger elimination of virus producing cells by cytolysis or host immune responses. However, studies revealed several limitations to this approach that require more investigation to assess its clinical application. Recent advances in gene editing technology prompted use of this approach for inactivating integrated proviral DNA in the genome of latently infected cells. This technology, which requires a detailed understanding of the viral genetics and robust delivery, may serve as a powerful strategy to eliminate the latent reservoir in the host leading to a sterile cure of AIDS.
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Details
- Title
- HIV-1 Latency and Eradication: Past, Present and Future
- Creators
- Prasun K. Datta - Temple Univ, Ctr Neurovirol, Dept Neurosci, 3500 N Broad St,7th Floor, Philadelphia, PA 19140 USARafal Kaminski - Temple Univ, Ctr Neurovirol, Dept Neurosci, 3500 N Broad St,7th Floor, Philadelphia, PA 19140 USAWenhui Hu - Temple Univ, Ctr Neurovirol, Dept Neurosci, 3500 N Broad St,7th Floor, Philadelphia, PA 19140 USAVanessa Pirrone - Drexel UniversityNeil T. Sullivan - Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Dept Microbiol & Immunol,Ctr Mol Virol & Translat, 245 N 15th St, Philadelphia, PA 19102 USAMichael R. Nonnemacher - Drexel UniversityWill Dampier - Drexel UniversityBrian Wigdahl - Drexel UniversityKamel Khalili - Temple University
- Publication Details
- Current HIV research, v 14(5), pp 431-441
- Publisher
- Bentham Science Publ Ltd
- Number of pages
- 11
- Grant note
- Public Health Service, National Institutes of Health; United States Department of Health & Human Services; United States Public Health Service; National Institutes of Health (NIH) - USA Department of Microbiology and Immunology 5T32MH079785 / National Institute of Mental Health under the Ruth L. Kirschstein National Research Service Award P30MH092177 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) DA19807; 5R01DA033213; 1P01DA037830-01A1 / National Institute of Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) Institute for Molecular Medicine and Infectious Disease P30 MH092177 / Comprehensive NeuroAIDS Center R01DA019807 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission NS32092; NS46263; NS089435 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01NS089435 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000388985500008
- Scopus ID
- 2-s2.0-84995546013
- Other Identifier
- 991019167613004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Virology