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Shilpee Sharma, Prabhu S Arunachalam, Malini Menon, Viswanath Ragupathy, Ravi Vijaya Satya, Joshua Jebaraj, Shambhu Ganeshappa Aralaguppe, Chaitra Rao, Sreshtha Pal, Shanmugam Saravanan, Kailapuri G Murugavel, Pachamuthu Balakrishnan, Suniti Solomon, Indira Hewlett, Udaykumar Ranga
HIV-1 subtype C (HIV-1C) may duplicate longer amino acid stretches in the p6 Gag protein, leading to the creation of an additional Pro-Thr/Ser-Ala-Pro (PTAP) motif necessary for viral packaging. However, the biological significance of a duplication of the PTAP motif for HIV-1 replication and pathogenesis has not been experimentally validated. In a longitudinal study of two different clinical cohorts of select HIV-1 seropositive, drug-naive individuals from India, we found that 8 of 50 of these individuals harbored a mixed infection of viral strains discordant for the PTAP duplication...
May 17, 2018: Journal of Biological Chemistry
Sharon Alroy-Preis, Elizabeth R Daly, Christine Adamski, Jodie Dionne-Odom, Elizabeth A Talbot, Fengxiang Gao, Steffany J Cavallo, Katrina Hansen, Jennifer C Mahoney, Erin Metcalf, Carol Loring, Christine Bean, Jan Drobeniuc, Guo-Liang Xia, Saleem Kamili, José T Montero
Background: In May 2012, the New Hampshire (NH) Division of Public Health Services (DPHS) was notified of 4 persons with newly diagnosed hepatitis C virus (HCV) infection at hospital X. Initial investigation suggested a common link to the hospital cardiac catheterization laboratory (CCL) because the infected persons included 3 CCL patients and a CCL technician. NH DPHS initiated an investigation to determine the source and control the outbreak. Methods: NH DPHS conducted site visits, case patient and employee interviews, medical record and medication use review, and employee and patient HCV testing using enzyme immunoassay for anti-HCV, reverse-transcription polymerase chain reaction for HCV RNA, nonstructural 5B (NS5B) and hypervariable region 1 (HVR1) sequencing, and quasispecies analysis...
May 14, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Hongshuo Song, Elena E Giorgi, Vitaly V Ganusov, Fangping Cai, Gayathri Athreya, Hyejin Yoon, Oana Carja, Bhavna Hora, Peter Hraber, Ethan Romero-Severson, Chunlai Jiang, Xiaojun Li, Shuyi Wang, Hui Li, Jesus F Salazar-Gonzalez, Maria G Salazar, Nilu Goonetilleke, Brandon F Keele, David C Montefiori, Myron S Cohen, George M Shaw, Beatrice H Hahn, Andrew J McMichael, Barton F Haynes, Bette Korber, Tanmoy Bhattacharya, Feng Gao
Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population...
May 15, 2018: Nature Communications
Václav Vopálenský, Anas Khawaja, Luděk Rožnovský, Jakub Mrázek, Tomáš Mašek, Martin Pospíšek
Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus from the genus Hepacivirus . The viral genomic +RNA is 9.6 kb long and contains highly structured 5' and 3' untranslated regions (UTRs) and codes for a single large polyprotein, which is co- and post-translationally processed by viral and cellular proteases into at least 11 different polypeptides. Most of the 5' UTR and an initial part of the polyprotein gene are occupied by an internal ribosome entry site (IRES), which mediates cap-independent translation of the viral proteins and allows the virus to overcome cellular antiviral defense based on the overall reduction of the cap-dependent translation initiation...
2018: Frontiers in Microbiology
Andri Taruna Rachmadi, Masaaki Kitajima, Kozo Watanabe, Sakiko Yaegashi, Joeselle Serrana, Arata Nakamura, Toyoko Nakagomi, Osamu Nakagomi, Kazuhiko Katayama, Satoshi Okabe, Daisuke Sano
Human noroviruses are excreted in feces from infected individuals and included in wastewater. It is critical to remove/inactivate them in wastewater treatment processes, particularly in the disinfection step, before release to water environments. However, the high mutation rate of human noroviruses raises concerns about the emergence of strains less susceptible to disinfectants that can survive even after wastewater treatment. This study aimed to prove the strain-dependent susceptibility of norovirus to free chlorine...
April 27, 2018: Applied and Environmental Microbiology
Li Qiu, Steven E Patterson, Laurent F Bonnac, Robert J Geraghty
Dengue virus affects millions of people worldwide each year. To date, there is no drug for the treatment of dengue-associated disease. Nucleosides are effective antivirals and work by inhibiting the accurate replication of the viral genome. Nucleobases offer a cheaper alternative to nucleosides for broad antiviral applications. Metabolic activation of nucleobases involves condensation with 5-phosphoribosyl-1-pyrophosphate to give the corresponding nucleoside-5'-monophosphate. This could provide an alternative to phosphorylation of a nucleoside, a step that is often rate limiting and inefficient in activation of nucleosides...
April 19, 2018: PLoS Neglected Tropical Diseases
Nontokozo D Matume, Denis M Tebit, Laurie R Gray, Marie-Louise Hammarskjold, David Rekosh, Pascal O Bessong
BACKGROUND: Entry inhibitors, such as Maraviroc, bind to CCR5 inhibiting entry of CCR5 utilizing viruses (R5 viruses). In the course of HIV infection, CXCR4 utilizing viruses (X4 viruses) may emerge and outgrow R5 viruses, and potentially limit the effectiveness of Maraviroc. The use of Maraviroc is reserved for salvage therapy in South Africa. OBJECTIVE: In this study, we examined the frequency of R5 and X4 viruses, using next generation sequencing, in patients under treatment to draw inferences on the utility of Maraviroc in a South African population...
February 15, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
H Fenaux, M Chassaing, S Berger, H Jeulin, A Gentilhomme, M Bensenane, J P Bronowicki, C Gantzer, I Bertrand, E Schvoerer
BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is emerging but its circulation between humans and the environment remains misunderstood. HEV ORF2 gene encodes the capsid playing a key role in viral interactions with surfaces, ORF3 products are involved in the viral cycle. Our aim was to study the molecular characteristics of ORF2 and ORF3 which could favor HEV fitness in patients and the environment. STUDY DESIGN: Samples from 69 patients with hepatitis (blood/stools), 20 urban wastewaters, 20 effluents of a pig slaughterhouse, 22 farm pigs (stools), 20 wild boars (liver/stools) were collected in North-Eastern France...
April 5, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Xin Wang, Wanyan Deng, Keli Qian, Haijun Deng, Yong Huang, Zeng Tu, Ailong Huang, Quanxin Long
Hepatitis B vaccination prevents 80-95% of transmission and reduces the incidence of HBV in children. The variations in the a determinant of HBV surface antigen (HBsAg) have been reported to be the most prevalent cause for vaccine or antibody escape. There is a conflicting evidence on as to whether escape mutants arise de novo in infected infants or whether the mutants, that have preexisted maternally, subsequently undergo selective replication in the infant under immune pressure. Here, we report that nearly 65% (55 of 85) vaccination failure in child patients has no amino acid substitution in a determinant as seen by Sanger sequencing...
April 8, 2018: European Journal of Clinical Microbiology & Infectious Diseases
Jiao Chen, Yingchao Zhao, Yanni Sun
Motivation: RNA virus populations contain different but genetically related strains, all infecting an individual host. Reconstruction of the viral haplotypes is a fundamental step to characterize the virus population, predict their viral phenotypes, and finally provide important information for clinical treatment and prevention. Advances of the next-generation sequencing technologies open up new opportunities to assemble full-length haplotypes. However, error-prone short reads, high similarities between related strains, an unknown number of haplotypes pose computational challenges for reference-free haplotype reconstruction...
April 3, 2018: Bioinformatics
Joseba Dalmau
We study Eigen's quasispecies model in the asymptotic regime where the length of the genotypes goes to [Formula: see text] and the mutation probability goes to 0. A limiting infinite system of differential equations is obtained. We prove convergence of trajectories, as well as convergence of the equilibrium solutions. We give analogous results for a discrete-time version of Eigen's model, which coincides with a model proposed by Moran.
April 2, 2018: Bulletin of Mathematical Biology
Xiuming Peng, Fumin Liu, Haibo Wu, Xiaorong Peng, Yufan Xu, Liyan Wang, Bin Chen, Tao Sun, Fan Yang, Shujing Ji, Nanping Wu
H5N6 avian influenza viruses (AIVs) can cause severe pneumonia and death in humans. However, the molecular determinants of H5N6 influenza virus mammalian adaption are still unclear. Three amino acid substitutions (HA A150V, PA A343T, PB2 E627K) are observed in H5N6 virus A/duck/Zhejiang/6D2/2013 (6D2) in lung-to-lung passage in mice. These substitutions are crucial to the pathogenicity of mouse-adapted virus. In this study, we investigated the contribution of each amino acid substitution in the virus by reverse genetics...
2018: Frontiers in Microbiology
Nonia Pariente
This month marks 40 years since the publication of 'Nucleotide sequence heterogeneity of an RNA phage population' in Cell. We spoke with Esteban Domingo, leading author of this landmark study carried out during his postdoctoral work in Charles Weissman's lab, which proposed RNA viral populations to be quasispecies.
April 2018: Nature Microbiology
Nastasja C Hauck, Josiane Kirpach, Christina Kiefer, Sophie Farinelle, Sophie Maucourant, Stephen A Morris, William Rosenberg, Feng Q He, Claude P Muller, I-Na Lu
To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH)...
March 25, 2018: Viruses
Yohei Watanabe, Yasuha Arai, Norihito Kawashita, Madiha S Ibrahim, Emad M Elgendy, Tomo Daidoji, Junichi Kajikawa, Hiroaki Hiramatsu, Nongluk Sriwilaijaroen, Takao Ono, Tatsuya Takagi, Kazuo Takahashi, Tatsuo Shioda, Kazuhiko Matsumoto, Yasuo Suzuki, Takaaki Nakaya
Transmission of avian influenza (AI) viruses to mammals involves phylogenetic bottlenecks that select small numbers of variants for transmission to new host species. However, little is known about the AI virus quasispecies diversity that produces variants for virus adaptation to humans. Here, we analyzed the hemagglutinin (HA) genetic diversity produced during AI H5N1 single-virus infection of primary human airway cells and characterized the phenotypes of these variants. During single-virus infection, HA variants emerged with increased fitness to infect human cells...
March 21, 2018: Journal of Virology
Almudena Cascajero, Alberto Rastrojo, Francisco Díez-Fuertes, Beatriz Hernández-Novoa, Begoña Aguado, Santiago Moreno, José Alcami, Mayte Pérez-Olmeda
In this study we have characterized quasispecies dynamics and the evolution of viral tropism in naive HIV-1-infected patients treated with a short-course of maraviroc monotherapy (NCT01060618) independently of their tropism. We randomly selected 20 patients displaying different basal tropism -10 R5 and 10 DMX4- at recruitment as determined by phenotypic tests (Trofile® ). Evolution of viral quasiespecies at the end of treatment was determined by ultra-deep sequencing of the V3 region using a 454 Life Sciences Platform and geno2pheno (g2p) algorithm for viral tropism prediction...
March 21, 2018: Journal of Virology
Adan Rios
There is consensus that only a preventive vaccine can contain the HIV/AIDS pandemic. After 30 years still there is no preventive HIV vaccine. This article examines fundamental challenges to the development of a preventive HIV vaccine. They include the initially erroneous but powerful perception of the natural history of HIV disease, as an acute rather than a chronic illness even in the absence of therapy, the lack of appreciation of the quasispecies biology of HIV and the abandonment of principles of immunology theory caused by the allure of technological prowess...
March 14, 2018: Current Opinion in Virology
Haijin Liu, Renata Servan de Almeida, Patricia Gil, Emmanuel Albina
Newcastle disease, caused by infection with virulent strains of Newcastle disease virus (NDV), poses a risk for the poultry industry. The virulence of NDV is mainly determined by the cleavage site of F protein. Lentogenic NDV can become velogenic after passages in SPF chicken brain and air sac based on some strains isolated from water birds, because the proportion of virulent-related strains gradually increases. In contrast, this proportion remains unchanged if NDV is passaged via 10-day-old SPF chicken embryos...
March 2018: Veterinary Microbiology
John S McCaskill
This contribution addresses the physical roles of spatial structures, either externally imposed or generated through self-assembly, either passive or active, on the physical chemistry of evolution. Starting with simple diffusion in closed capillaries, a one-dimensional space, it covers eight aspects of experimental and theoretical research into the interaction of evolution with spatial structures: in various dimensions, including hitherto unexplored ones, spanning from externally defined physical spaces to actively tailored spaces, assembled by the evolving components themselves...
March 2, 2018: European Biophysics Journal: EBJ
Aysan Ghasemzadeh, Marta Małgorzata Ter Haar, Masoud Shams-Bakhsh, Walter Pirovano, Vitantonio Pantaleo
Next-generation sequencing has opened the door to the reconstruction of viral populations and examination of the composition of mutant spectra in infected cells, tissues, and host organisms. In this chapter we present details on the use of the Shannon entropy method to estimate the site-specific nucleotide relative variability of turnip crinkle virus, a positive (+) stranded RNA plant virus, in a large dataset of short RNAs of Cicer arietinum L., a natural reservoir of the virus. We propose this method as a viral metagenomics tool to provide a more detailed description of the viral quasispecies in infected plant tissue...
2018: Methods in Molecular Biology
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