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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Genetic variation and function of the HIV-1 Tat protein
Medical microbiology and immunology, v 208(2), pp 131-169
01 Apr 2019
PMID: 30834965
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human immunodeficiency virus type 1 (HIV-1) encodes a transactivator of transcription (Tat) protein, which has several functions that promote viral replication, pathogenesis, and disease. Amino acid variation within Tat has been observed to alter the functional properties of Tat and, depending on the HIV-1 subtype, may produce Tat phenotypes differing from viruses’ representative of each subtype and commonly used in in vivo and in vitro experimentation. The molecular properties of Tat allow for distinctive functional activities to be determined such as the subcellular localization and other intracellular and extracellular functional aspects of this important viral protein influenced by variation within the Tat sequence. Once Tat has been transported into the nucleus and becomes engaged in transactivation of the long terminal repeat (LTR), various Tat variants may differ in their capacity to activate viral transcription. Post-translational modification patterns based on these amino acid variations may alter interactions between Tat and host factors, which may positively or negatively affect this process. In addition, the ability of HIV-1 to utilize or not utilize the transactivation response (TAR) element within the LTR, based on genetic variation and cellular phenotype, adds a layer of complexity to the processes that govern Tat-mediated proviral DNA-driven transcription and replication. In contrast, cytoplasmic or extracellular localization of Tat may cause pathogenic effects in the form of altered cell activation, apoptosis, or neurotoxicity. Tat variants have been shown to differentially induce these processes, which may have implications for long-term HIV-1-infected patient care in the antiretroviral therapy era. Future studies concerning genetic variation of Tat with respect to function should focus on variants derived from HIV-1-infected individuals to efficiently guide Tat-targeted therapies and elucidate mechanisms of pathogenesis within the global patient population.
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Details
- Title
- Genetic variation and function of the HIV-1 Tat protein
- Creators
- Cassandra Spector - Drexel UniversityAnthony R. Mele - Drexel UniversityBrian Wigdahl - Drexel UniversityMichael R. Nonnemacher - Drexel University
- Publication Details
- Medical microbiology and immunology, v 208(2), pp 131-169
- Publisher
- Springer Berlin Heidelberg
- Grant note
- R01 NS089435 / National Institute of Neurological Disorders and Stroke (http://dx.doi.org/10.13039/100000065) P30 MH092177; T32 MH079785 / National Institute of Mental Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000463234300001
- Scopus ID
- 2-s2.0-85062696370
- Other Identifier
- 991019168735204721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Microbiology