Article ; Online: Mechanistic Interplay between HIV-1 Reverse Transcriptase Enzyme Kinetics and Host SAMHD1 Protein: Viral Myeloid-Cell Tropism and Genomic Mutagenesis.
2022 Volume 14, Issue 8
Abstract: 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, ... ...
| Abstract | 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. |
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| MeSH term(s) | Antiviral Agents/pharmacology ; DNA-Directed DNA Polymerase/genetics ; Genomics ; HIV Reverse Transcriptase/genetics ; HIV Reverse Transcriptase/metabolism ; HIV-1/genetics ; HIV-1/metabolism ; Humans ; Mutagenesis ; Myeloid Cells/metabolism ; SAM Domain and HD Domain-Containing Protein 1/genetics ; SAM Domain and HD Domain-Containing Protein 1/metabolism ; Viral Tropism ; Virus Replication |
| Chemical Substances | Antiviral Agents ; reverse transcriptase, Human immunodeficiency virus 1 (EC 2.7.7.-) ; HIV Reverse Transcriptase (EC 2.7.7.49) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; SAM Domain and HD Domain-Containing Protein 1 (EC 3.1.5.-) ; SAMHD1 protein, human (EC 3.1.5.-) |
| Language | English |
| Publishing date | 2022-07-26 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Review ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2516098-9 |
| ISSN | 1999-4915 ; 1999-4915 |
| ISSN (online) | 1999-4915 |
| ISSN | 1999-4915 |
| DOI | 10.3390/v14081622 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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