Defective Strand-Displacement DNA Synthesis Due to Accumulation of Thymidine Analogue Resistance Mutations in HIV-2 Reverse Transcriptase.

ACS Infectious Diseases
Samara Martín-AlonsoLuis Menéndez-Arias

Abstract

Retroviral reverse transcriptases (RTs) have the ability to carry out strand displacement DNA synthesis in the absence of accessory proteins. Although studies with RTs and other DNA polymerases suggest that fingers subdomain residues participate in strand displacement, molecular determinants of this activity are still unknown. A mutant human immunodeficiency virus type 2 (HIV-2) RT (M41L/D67N/K70R/S215Y) with low strand displacement activity was identified after screening a panel of purified enzymes, including several antiretroviral drug-resistant HIV-1 and HIV-2 RTs. In HIV-1, resistance to zidovudine and other thymidine analogues is conferred by different combinations of M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q (designated as thymidine analogue resistance-associated mutations (TAMs)). However, those changes are rarely selected in HIV-2. We show that the strand displacement activity of HIV-2ROD mutants M41L/S215Y and D67N/K70R was only slightly reduced compared to the wild-type RT. In contrast, mutants D67N/K70R/S215Y and M41L/D67N/K70R/S215Y were the most defective RTs in reactions carried out with nicked and gapped substrates. Moreover, these enzymes showed the lowest nucleotide incorporation rates in assays carried out...Continue Reading

References

Sep 2, 1994·Journal of Molecular Biology·P CharneauF Clavel
Jan 26, 1996·The Journal of Biological Chemistry·G M FuentesR A Bambara
May 23, 1998·The Journal of Biological Chemistry·C D Kelleher, J J Champoux
Apr 7, 2004·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Thomas A Steitz, Y Whitney Yin
Nov 19, 2004·The Biochemical Journal·Clara E Cases-González, Luis Menéndez-Arias
Jan 30, 2007·The Journal of Biological Chemistry·Kamalendra SinghMukund J Modak
Oct 16, 2007·Journal of Molecular Biology·Anna Kurzynska-KokorniakThomas H Eickbush
Oct 7, 2008·The Journal of Biological Chemistry·Peter M J Burgers
Jan 16, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Geoffrey S GottliebUNKNOWN University of Washington-Dakar HIV-2 Study Group
May 12, 2011·The Journal of Antimicrobial Chemotherapy·Ana TreviñoUNKNOWN HIV-2 Spanish Study Group
Dec 3, 2013·Journal of Immunological Methods·Marcella Sarzotti-KelsoeDavid C Montefiori
Dec 19, 2013·Antiviral Research·Luis Menéndez-Arias, Mar Alvarez
Dec 29, 2013·Journal of Virology·Redmond P SmythMiles P Davenport
Jan 21, 2014·Experimental Cell Research·Erwin L van DijkClaude Thermes
Mar 4, 2014·AIDS·Charlotte CharpentierUNKNOWN IeDEA West Africa Collaboration
Jun 19, 2014·Current Protocols in Bioinformatics·David H Mathews
Jun 25, 2015·Microbiology Spectrum·Stephen H Hughes
Nov 9, 2016·Frontiers in Cell and Developmental Biology·Ping HuGlenn Deng
Jan 4, 2017·Virus Research·Luis Menéndez-AriasMar Álvarez
Mar 17, 2017·Annual Review of Biochemistry·Peter M J Burgers, Thomas A Kunkel

❮ Previous
Next ❯

Citations

Jul 13, 2020·Trends in Biotechnology·Samara Martín-AlonsoLuis Menéndez-Arias

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.