Mechanistic Interplay between HIV-1 Reverse Transcriptase Enzyme Kinetics and Host SAMHD1 Protein: Viral Myeloid-Cell Tropism and Genomic Mutagenesis

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been the primary interest among studies on antiviral discovery, viral replication kinetics, drug resistance, and viral evolution. Following infection and entry into target cells, the HIV-1 core disassembles, and the viral RT...

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Vydané v:	Viruses Ročník 14; číslo 8; s. 1622
Hlavní autori:	Bowen, Nicole E., Oo, Adrian, Kim, Baek
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland MDPI AG 26.07.2022 MDPI
Predmet:	Antiretroviral drugs antiretroviral therapy Antiviral Agents - pharmacology Antiviral drugs Binding sites Deoxyribonucleic acid DNA DNA polymerase DNA-directed DNA polymerase DNA-Directed DNA Polymerase - genetics Double-stranded RNA Drug resistance Enzyme kinetics evolution Exonuclease Genetic aspects genome Genomes Genomics HIV HIV (Viruses) HIV Reverse Transcriptase - genetics HIV Reverse Transcriptase - metabolism HIV-1 - genetics HIV-1 - metabolism Human immunodeficiency virus Human immunodeficiency virus 1 human immunodeficiency virus type 1 Humans Immune system Infections Life cycles Lymphocytes Methods Mutagenesis Mutation Myeloid cells Myeloid Cells - metabolism Proofreading Proteins Replication retrovirus reverse transcriptase Review RNA RNA-directed DNA polymerase SAM Domain and HD Domain-Containing Protein 1 - genetics SAM Domain and HD Domain-Containing Protein 1 - metabolism therapeutics Tropism Viral Tropism Virus Replication Viruses United States human immunodeficiency virus type 1 mutation retrovirus reverse transcriptase antiretroviral therapy drug resistance SAMHD1 cell tropism
ISSN:	1999-4915, 1999-4915
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Popis
Shrnutí:	Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been the primary interest among studies on antiviral discovery, viral replication kinetics, drug resistance, and viral evolution. Following infection and entry into target cells, the HIV-1 core disassembles, and the viral RT concomitantly converts the viral RNA into double-stranded proviral DNA, which is integrated into the host genome. The successful completion of the viral life cycle highly depends on the enzymatic DNA polymerase activity of RT. Furthermore, HIV-1 RT has long been known as an error-prone DNA polymerase due to its lack of proofreading exonuclease properties. Indeed, the low fidelity of HIV-1 RT has been considered as one of the key factors in the uniquely high rate of mutagenesis of HIV-1, which leads to efficient viral escape from immune and therapeutic antiviral selective pressures. Interestingly, a series of studies on the replication kinetics of HIV-1 in non-dividing myeloid cells and myeloid specific host restriction factor, SAM domain, and HD domain-containing protein, SAMHD1, suggest that the myeloid cell tropism and high rate of mutagenesis of HIV-1 are mechanistically connected. Here, we review not only HIV-1 RT as a key antiviral target, but also potential evolutionary and mechanistic crosstalk among the unique enzymatic features of HIV-1 RT, the replication kinetics of HIV-1, cell tropism, viral genetic mutation, and host SAMHD1 protein.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 These authors contributed equally to this work.
ISSN:	1999-4915 1999-4915
DOI:	10.3390/v14081622