Special Issue "Retroviral Enzymes"

Guest Editor
Dr. Luis Menéndez-Arias
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
Website: http://www2.cbm.uam.es/mkfactory.esdomain/webs/CBMSO/plt_LineasInvestigacion.aspx?IdObjeto=22
E-Mail:
Interests: HIV; reverse transcription; drug resistance; genetic variation; proteolytic processing; HIV protease

Short summary

The retroviral RNA genome encodes for three enzymes essential for virus replication: (i) the viral protease (PR), that converts the immature virion into a mature virus through the cleavage of precursor polypeptides; (ii) the reverse transcriptase (RT), responsible for the conversion of the single-stranded genomic RNA into double-stranded proviral DNA; and (iii) the integrase (IN) that inserts the proviral DNA into the host cell genome. All of them are important targets for therapeutic intervention. Knowledge on their structure and mechanism of action should help us to design better drugs against AIDS and other diseases caused by retroviruses.

Dr. Luis Menéndez-Arias
Guest Editor

Submission Information

All papers should be submitted to viruses@mdpi.org. To be published continuously until the deadline and papers will be listed together at the special issue website.

Submitted papers should not have been published nor be under consideration for publication elsewhere. All papers are refereed through a peer-review process. A guide for authors is available on the Instructions for Authors page. Viruses is a new international, peer-reviewed, quarterly open access journal published by Molecular Diversity Preservation International.

Article Processing Charges (APC) for publication in this Open Access journal are waived for well-prepared manuscripts submitted by 30 June 2010. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• Aspartyl-proteases
• Reverse transcription
• Integration
• Virus maturation
• Antiretroviral drugs
• Drug targets
• Viral mutation and variability

Type of Paper: Review
Title: The retroviral DNA Synthesis Machinery
Author: Jean-Luc Darlix and Francoise Barré-Sinoussi
E-Mails: jldarlix@ens-lyon.fr, fbarre@pasteur.fr
Abstract: Reverse transcription is an obligatory step during replication and amplification of retroviruses and retrotransposons, respectively. The reverse transcription process is a complex series of reactions during which the retroviral RNA/DNA dependent DNA polymerase, or reverse transcriptase (RT), copies the single stranded RNA of the viral genome to generate the double stranded proviral DNA, while the viral RNA template is being degraded by the RT-RNase H. Synthesis of the complete proviral DNA, flanked by the two long terminal repeats (LTR), necessitates two viral DNA strand transfers, that are achieved by the hybridization of complementary sequences in the viral nucleic acids. To this end the RT RNase H activity removes segments of the RNA template strand from the growing DNA strand, freeing a single stranded region to be annealed to the complementary sequence, a reaction chaperoned by the viral nucleocapsid protein (NC). Two copies of the genomic RNA, sometimes different in case of co-infection with HIV-1 variants, are packaged in the form of a 60S complex in virions produced by infected cells. Properties of the reverse transcription (RTion) machinery - RT, the genomic RNA and NC - allow a transfer of the growing DNA strand between the two viral RNA templates to occur at any point during RTion, resulting in the production of recombinant virus progeny. Such recombination reactions promote genotypic and phenotypic diversities of the virus population that help it to escape, at least in part, the host immune defenses and drug therapies.
This short review summarizes the complex process of reverse transcription, with a special emphasis on the interplay between the RT enzyme and specific signals along the genomic RNA, as well as with essential cofactors such as the nucleocapsid protein (NC). Since the physiological conditions can impact on the process of reverse transcription, a special attention is put on how factors present in the intra-cellular or extra-cellular milieu can drastically influence the level and timing ofreverse transcription and hence virus infectivity.

Type of Paper: Review
Title: RNase H structure, catalytic mechanism and inhibitors
Author: Matthias Götte
E-Mail: matthias.gotte@mcgill.ca
Abstract: to be added soon

Type of Paper: Review
Authors: B. Studamire; S.P. Goff
E-Mail: bstudamire@brooklyn.cuny.edu
Title: Interactions of host proteins with the MLV integrase-
Abstract: Retroviral infections cause a variety of cancers in animals and a number of diverse diseases in humans such as leukemia and acquired immune deficiency syndrome. Productive and efficient proviral integration is critical for retroviral function and is the key step in establishing a stable and productive infection. Host factors are proposed to be involved in all stages of the retroviral life cycle, and the identification of integrase interacting factors has the potential to increase our understanding of mechanisms by which the incoming virus might appropriate cellular proteins to target and capture host DNA sequences. Identification of MoMLV integrase interacting host factors may be key to designing efficient and benign retroviral-based gene therapy vectors; key to understanding the basic mechanism of integration; and key in designing efficient integrase inhibitors. In this review, we discuss current progress in the field of MoMLV integrase interacting proteins and possible roles for these proteins in integration.