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HIV molecular evolution

Dan-Dan He, Yueer Lu, Rachel Gittelman, Yabin Jin, Fei Ling, Akey Joshua
Viral selection pressure has acted on restriction factors that play an important role in the innate immune system by inhibiting the replication of viruses during primate evolution. Tripartite motif-containing (TRIM) family members are some of these restriction factors. It is becoming increasingly clear that gene expression differences, rather than protein-coding regions changes, could play a vital role in the anti-retroviral immune mechanism. Increasingly, recent studies have created genome-scale catalogues of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA...
October 12, 2016: Proceedings. Biological Sciences
Barbara Van Der Pol
HSV-1 and HSV-2 are among the most common causes of sexually transmitted infections (stis) globally. these infections are strongly associated with increased risk of hiv acquisition and rare, but devastating, neonatal disease. available treatment options can reduce HSV transmission and improve quality of life. accurate diagnosis early in disease can improve patient management. Areas covered: This paper describes the clinical manifestations of HSV infection often used for clinical diagnostic purposes. The paper then describes the evolution of laboratory diagnostic assays...
October 8, 2016: Expert Review of Molecular Diagnostics
Robert Polster, Christos J Petropoulos, Sebastian Bonhoeffer, Frédéric Guillaume
The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to fully explore that link and tend to show poor correspondence between modular structures within the GP map and among phenotypes...
September 27, 2016: Molecular Biology and Evolution
Sushama Telwatte, Chanson J Brumme, Anna C Hearps, Catherine F Latham, Joshua A Hayward, Secondo Sonza, Nicolas Sluis-Cremer, P Richard Harrigan, Gilda Tachedjian
OBJECTIVE: Synonymous substitutions K65K or K66K in HIV-1 reverse transcriptase (RT) alleviate fitness and fidelity defects in HIV-1 molecular clones harboring thymidine analog mutations (TAMs); however their potential for transmission and persistence is unknown. Here we investigated the temporal appearance of K65K/K66K relative to TAMs in a HIV-1 cohort, their prevalence over time, and their impact on viral fitness in the context of patient-derived RT sequences. METHODS: Retrospective analyses of the temporal appearance and longitudinal prevalence of synonymous substitutions and drug resistance mutations were performed using the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP) database...
September 24, 2016: AIDS
Disha Patel, Janet Antwi, Pratibha C Koneru, Erik Serrao, Stefano Forli, Jacques J Kessl, Lei Feng, Nanjie Deng, Ronald M Levy, James R Fuchs, Arthur J Olson, Alan N Engelman, Joseph D Bauman, Mamuka Kvaratskhelia, Eddy Arnold
HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials. ALLINIs exhibit a multimodal mechanism of action by inducing aberrant IN multimerization during virion morphogenesis and by competing with IN for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection. However, quinoline-based ALLINIs impose a low genetic barrier for the evolution of resistant phenotypes, which highlights a need for discovery of second-generation inhibitors...
September 19, 2016: Journal of Biological Chemistry
Jayna Raghwani, Rebecca Rose, Isabelle Sheridan, Philippe Lemey, Marc A Suchard, Teresa Santantonio, Patrizia Farci, Paul Klenerman, Oliver G Pybus
The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens...
September 2016: PLoS Pathogens
Olga S Voitenko, Andi Dhroso, Anna Feldmann, Dmitry Korkin, Olga V Kalinina
MOTIVATION: Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity...
September 1, 2016: Bioinformatics
Yaqiong Wang, Zekun Wang, Ankita Pramanik, Mario L Santiago, Jianming Qiu, Edward B Stephens
Old World monkey (OWM) and hominid APOBEC3Aproteins exhibit differential restriction activities against lentiviruses and DNA viruses. Human APOBEC3A(hA3A)has weak restriction activity against HIV-1Δvifbut is efficiently restricted by an artificially generated chimeric from mandrills (mndA3A/G). We show that a chimeric hA3Acontaining the "WVS" insertion (hA3A[(27)WVS(29)]) conferred potent HIV-1restriction activity. Analysis of each amino acid of the "WVS" motif show that the length and not necessarily the charge or hydrophobicity of the amino acids accounted for restriction activity...
November 2016: Virology
Ana C P Souto, Lucas X Bonfietti, Kennio Ferreira-Paim, Luciana Trilles, Marilena Martins, Marcelo Ribeiro-Alves, Cau D Pham, Liline Martins, Wallace Dos Santos, Marilene Chang, Fabio Brito-Santos, Dayane C S Santos, Silvana Fortes, Shawn R Lockhart, Bodo Wanke, Márcia S C Melhem, Márcia S Lazéra, Wieland Meyer
Cryptococcus neoformans and Cryptococcus gattii are responsible globally for almost one million cryptococcosis cases yearly, mostly in immunocompromised patients, such as those living with HIV. Infections due to C. gattii have mainly been described in tropical and subtropical regions, but its adaptation to temperate regions was crucial in the species evolution and highlighted the importance of this pathogenic yeast in the context of disease. Cryptococcus gattii molecular type VGII has come to the forefront in connection with an on-going emergence in the Pacific North West of North America...
August 2016: PLoS Neglected Tropical Diseases
Marion Cornelissen, Astrid Gall, Monique Vink, Fokla Zorgdrager, Špela Binter, Stephanie Edwards, Suzanne Jurriaans, Margreet Bakker, Swee Hoe Ong, Luuk Gras, Ard van Sighem, Daniela Bezemer, Frank de Wolf, Peter Reiss, Paul Kellam, Ben Berkhout, Christophe Fraser, Antoinette C van der Kuyl
The BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) project aims to analyse nearly-complete viral genomes from >3000 HIV-1 infected Europeans using high-throughput deep sequencing techniques to investigate the virus genetic contribution to virulence. Following the development of a computational pipeline, including a new de novo assembler for RNA virus genomes, to generate larger contiguous sequences (contigs) from the abundance of short sequence reads that characterise the data, another area that determines genome sequencing success is the quality and quantity of the input RNA...
August 4, 2016: Virus Research
Supreet Kaur Gill, Ajay Francis Christopher, Vikas Gupta, Parveen Bansal
Clinical research is making toiling efforts for promotion and wellbeing of the health status of the people. There is a rapid increase in number and severity of diseases like cancer, hepatitis, HIV etc, resulting in high morbidity and mortality. Clinical research involves drug discovery and development whereas clinical trials are performed to establish safety and efficacy of drugs. Drug discovery is a long process starting with the target identification, validation and lead optimization. This is followed by the preclinical trials, intensive clinical trials and eventually post marketing vigilance for drug safety...
July 2016: Perspectives in Clinical Research
Zeli Zhang, Qinyong Gu, Ananda Ayyappan Jaguva Vasudevan, Anika Hain, Björn-Philipp Kloke, Sascha Hasheminasab, Daniel Mulnaes, Kei Sato, Klaus Cichutek, Dieter Häussinger, Ignacio G Bravo, Sander H J Smits, Holger Gohlke, Carsten Münk
BACKGROUND: Feline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion called linker...
2016: Retrovirology
Ben Murrell, Thomas Vollbrecht, John Guatelli, Joel O Wertheim
UNLABELLED: Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles...
September 15, 2016: Journal of Virology
Apostolos Beloukas, Alexandros Psarris, Polina Giannelou, Evangelia Kostaki, Angelos Hatzakis, Dimitrios Paraskevis
Human Immunodeficiency Virus type 1 (HIV-1) is characterised by vast genetic diversity. Globally circulating HIV-1 viruses are classified into distinct phylogenetic strains (subtypes, sub-subtypes) and several recombinant forms. Here we describe the characteristics and evolution of European HIV-1 epidemic over time through a review of published literature and updated queries of existing HIV-1 sequence databases. HIV-1 in Western and Central Europe was introduced in the early-1980s in the form of subtype B, which is still the predominant clade...
June 16, 2016: Infection, Genetics and Evolution
Uddhav Timilsina, Dibya Ghimire, Bivek Timalsina, Theodore J Nitz, Carl T Wild, Eric O Freed, Ritu Gaur
Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR)...
2016: Scientific Reports
Sung Yong Park, Tanzy M T Love, Alan S Perelson, Wendy J Mack, Ha Youn Lee
BACKGROUND: The molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1's early evolution in the presence of immune selection has not yet been fully examined. RESULTS: We identified molecular clock signatures from 1587 previously published HIV-1 full envelope gene sequences obtained since acute infection in 15 subjects...
2016: Retrovirology
Edina Amponsah-Dacosta, J Nare Rakgole, Maemu P Gededzha, Azwidowi Lukhwareni, Jason T Blackard, Selokela G Selabe, M Jeffrey Mphahlele
BACKGROUND: Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa. MATERIALS AND METHODS: This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined...
September 2016: Infection, Genetics and Evolution
Anjali Verma, Pavithra Rajagopalan, Rishikesh Lotke, Rebu Varghese, Deepak Selvam, Tapas K Kundu, Udaykumar Ranga
UNLABELLED: Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-κB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-associated variations in the core transcription factor binding sites (TFBS) influence gene expression from the viral promoter has not been examined previously...
August 15, 2016: Journal of Virology
Luke I Rast, Igor M Rouzine, Ganna Rozhnova, Lisa Bishop, Ariel D Weinberger, Leor S Weinberger
The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines. Previously, it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual patients, these engineered molecular parasites were further predicted to be refractory to HIV's mutational escape (i.e., be 'resistance-proof'). However, an outstanding question has been whether these engineered interfering particles-termed Therapeutic Interfering Particles (TIPs)-would remain resistance-proof at the population-scale, where TIP-resistant HIV mutants may transmit more efficiently by reaching higher viral loads in the TIP-treated subpopulation...
May 2016: PLoS Computational Biology
Jie Zhang, Xiang Gao, John Martin, Bruce Rosa, Zheng Chen, Makedonka Mitreva, Timothy Henrich, Daniel Kuritzkes, Lee Ratner
The HIV-1 envelope interacts with coreceptors CCR5 and CXCR4 in a dynamic, multi-step process, its molecular details not clearly delineated. Use of CCR5 antagonists results in tropism shift and therapeutic failure. Here we describe a novel approach using full-length patient-derived gp160 quasispecies libraries cloned into HIV-1 molecular clones, their separation based on phenotypic tropism in vitro, and deep sequencing of the resultant variants for structure-function analyses. Analysis of functionally validated envelope sequences from patients who failed CCR5 antagonist therapy revealed determinants strongly associated with coreceptor specificity, especially at the gp120-gp41 and gp41-gp41 interaction surfaces that invite future research on the roles of subunit interaction and envelope trimer stability in coreceptor usage...
July 2016: Virology
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