Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.1
4.7
Journals
Viruses
Special Issues
Viral Reverse Transcriptases
share announcement

Viral Reverse Transcriptases

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 6297

Special Issue Editor

Dr. Luis Menéndez-Arias

E-Mail Website
Guest Editor
Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, c/ Nicolás Cabrera 1, Campus de Cantoblanco, 28049 Madrid, Spain
Interests: HIV; reverse transcription; drug resistance; genetic variation; proteolytic processing; HIV protease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fifty years ago, the discovery of reverse transcriptases in retroviruses (then known as RNA tumor viruses) by David Baltimore and Howard Temin was a major breakthrough that revolutionized molecular biology and established the foundations of retrovirology and cancer biology while providing opportunity for the development of novel biotechnological methods with wide applications in life sciences. Reverse transcriptases are nucleic acid polymerases that synthesize DNA using RNA as a template. They play a pivotal role in the replication of several virus families, most notably Retroviridae and Hepadnaviridae. HIV-1 reverse transcriptase inhibitors acting on its polymerase activity constitute the backbone of currently prescribed antiretroviral therapies. Several nucleoside analogue inhibitors of the viral reverse transcriptase are also widely used in the treatment of chronic hepatitis B. Moreover, human endogenous retroviruses make up 8% of the human genome and encode reverse transcriptases, although their contribution to human health is poorly understood and understudied.

This Special Issue invites articles and reviews that focus on the structures of viral reverse transcriptases, their mechanisms of action, their interaction with viral and host factors and their contribution to viral evolution, as well as research in the design and development of antiviral agents targeting viral reverse transcriptases, and novel biotechnological methods and uses of those enzymes in basic and clinical virology.

Dr. Luis Menéndez-Arias
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • reverse transcription
  • retrovirus
  • HIV
  • hepatitis B virus
  • DNA polymerase
  • ribonuclease H
  • antiviral therapy
  • virus evolution

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 3198 KiB  
Article
Cis-Allosteric Regulation of HIV-1 Reverse Transcriptase by Integrase
by Takao Masuda, Osamu Kotani, Masaru Yokoyama, Yuya Abe, Gota Kawai and Hironori Sato
Viruses 2023, 15(1), 31; https://doi.org/10.3390/v15010031 - 21 Dec 2022
Cited by 2 | Viewed by 1258
Abstract
Reverse transcriptase (RT) and integrase (IN) are encoded tandemly in the pol genes of retroviruses. We reported recently that HIV-1 RT and IN need to be supplied as the pol precursor intermediates, in which RT and IN are in fusion form (RTIN) to [...] Read more.
Reverse transcriptase (RT) and integrase (IN) are encoded tandemly in the pol genes of retroviruses. We reported recently that HIV-1 RT and IN need to be supplied as the pol precursor intermediates, in which RT and IN are in fusion form (RTIN) to exert efficient reverse transcription in the context of HIV-1 replication. The mechanism underlying RTIN’s effect, however, remains to be elucidated. In this study, we examined the effect of IN fusion on RT during reverse transcription by an in vitro cell-free assay, using recombinant HIV-1 RTIN (rRTIN). We found that, compared to recombinant RT (rRT), rRTIN generated significantly higher cDNAs under physiological concentrations of dNTPs (less than 10 μM), suggesting increased affinity of RTIN to dNTPs. Importantly, the cleavage of RTIN with HIV-1 protease reduced cDNA levels at a low dose of dNTPs. Similarly, sensitivities against RT inhibitors were significantly altered in RTIN form. Finally, analysis of molecular dynamics simulations of RT and RTIN suggested that IN can influence the structural dynamics of the RT active center and the inhibitor binding pockets in cis. Thus, we demonstrated, for the first time, the cis-allosteric regulatory roles of IN in RT structure and enzymatic activity. Full article
(This article belongs to the Special Issue Viral Reverse Transcriptases)
►▼ Show Figures

Figure 1

Review

Jump to: Research

40 pages, 10519 KiB  
Review
Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
by Murugesan Vanangamudi, Senthilkumar Palaniappan, Muthu Kumaradoss Kathiravan and Vigneshwaran Namasivayam
Viruses 2023, 15(10), 1992; https://doi.org/10.3390/v15101992 - 25 Sep 2023
Viewed by 1971
Abstract
AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the [...] Read more.
AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the discovery of the first drug, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), to date, 30 drugs have been approved by the FDA, primarily targeting reverse transcriptase, integrase, and/or protease enzymes. The majority of these drugs target the catalytic and allosteric sites of the HIV enzyme reverse transcriptase. Compared to the NRTI family of drugs, the diverse chemical class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) has special anti-HIV activity with high specificity and low toxicity. However, current clinical usage of NRTI and NNRTI drugs has limited therapeutic value due to their adverse drug reactions and the emergence of multidrug-resistant (MDR) strains. To overcome drug resistance and efficacy issues, combination therapy is widely prescribed for HIV patients. Combination antiretroviral therapy (cART) includes more than one antiretroviral agent targeting two or more enzymes in the life cycle of the virus. Medicinal chemistry researchers apply different optimization strategies including structure- and fragment-based drug design, prodrug approach, scaffold hopping, molecular/fragment hybridization, bioisosterism, high-throughput screening, covalent-binding, targeting highly hydrophobic channel, targeting dual site, and multi-target-directed ligand to identify and develop novel NNRTIs with high antiviral activity against wild-type (WT) and mutant strains. The formulation experts design various delivery systems with single or combination therapies and long-acting regimens of NNRTIs to improve pharmacokinetic profiles and provide sustained therapeutic effects. Full article
(This article belongs to the Special Issue Viral Reverse Transcriptases)
►▼ Show Figures

Graphical abstract

22 pages, 1423 KiB  
Review
Mechanistic Interplay between HIV-1 Reverse Transcriptase Enzyme Kinetics and Host SAMHD1 Protein: Viral Myeloid-Cell Tropism and Genomic Mutagenesis
by Nicole E. Bowen, Adrian Oo and Baek Kim
Viruses 2022, 14(8), 1622; https://doi.org/10.3390/v14081622 - 26 Jul 2022
Cited by 4 | Viewed by 2276
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Viral Reverse Transcriptases)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop