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1.
Viruses ; 16(3)2024 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-38543738

RESUMEN

Influenza D virus (IDV) is the most recent addition to the Orthomyxoviridae family and cattle serve as the primary reservoir. IDV has been implicated in Bovine Respiratory Disease Complex (BRDC), and there is serological evidence of human infection of IDV. Evolutionary changes in the IDV genome have resulted in the expansion of genetic diversity and the emergence of multiple lineages that might expand the host tropism and potentially increase the pathogenicity to animals and humans. Therefore, there is an urgent need for automated, accurate and rapid typing tools for IDV lineage typing. Currently, IDV lineage typing is carried out using BLAST-based searches and alignment-based molecular phylogeny of the hemagglutinin-esterase fusion (HEF) gene sequences, and lineage is assigned to query sequences based on sequence similarity (BLAST search) and proximity to the reference lineages in the tree topology, respectively. To minimize human intervention and lineage typing time, we developed IDV Typer server, implementing alignment-free method based on return time distribution (RTD) of k-mers. Lineages are assigned using HEF gene sequences. The server performs with 100% sensitivity and specificity. The IDV Typer server is the first application of an RTD-based alignment-free method for typing animal viruses.


Asunto(s)
Infecciones por Orthomyxoviridae , Orthomyxoviridae , Thogotovirus , Humanos , Animales , Bovinos , Deltainfluenzavirus , Thogotovirus/genética
2.
Viruses ; 13(11)2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34835044

RESUMEN

The COVID-19 pandemic is a global challenge that impacted 200+ countries. India ranks in the second and third positions in terms of number of reported cases and deaths. Being a populous country with densely packed cities, SARS-CoV-2 spread exponentially. India sequenced ≈0.14% isolates from confirmed cases for pandemic surveillance and contributed ≈1.58% of complete genomes sequenced globally. This study was designed to map the circulating lineage diversity and to understand the evolution of SARS-CoV-2 in India using comparative genomics and population genetics approaches. Despite varied sequencing coverage across Indian States and Union Territories, isolates belonging to variants of concern (VoC) and variants of interest (VoI) circulated, persisted, and diversified during the first seventeen months of the pandemic. Delta and Kappa lineages emerged in India and spread globally. The phylogenetic tree shows lineage-wise monophyletic clusters of VoCs/VoIs and diversified tree topologies for non-VoC/VoI lineages designated as 'Others' in this study. Evolutionary dynamics analyses substantiate a lack of spatio-temporal clustering, which is indicative of multiple global and local introductions. Sites under positive selection and significant variations in spike protein corroborate with the constellation of mutations to be monitored for VoC/VoI as well as substitutions that are characteristic of functions with implications in virus-host interactions, differential glycosylation, immune evasion, and escape from neutralization.


Asunto(s)
COVID-19/virología , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/epidemiología , Evolución Molecular , Genoma Viral , Humanos , India/epidemiología , Modelos Moleculares , Mutación , Filogenia , Conformación Proteica , Dominios Proteicos , SARS-CoV-2/aislamiento & purificación , Selección Genética , Glicoproteína de la Espiga del Coronavirus/química , Secuenciación Completa del Genoma
3.
Vaccine ; 39(6): 876-881, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33423836

RESUMEN

Rubella, is a contagious disease caused by Rubella virus (RuV) that manifests as fever with skin-rashes in children and adults along with complications in pregnant women. WHO-SEAR has set a target for Rubella elimination by 2023. This is the first report of antigenic characterization and genome sequencing of nine RuVs sampled during 1992, 2007-9, and 2015-17 from four Indian states. Comparative analysis of Indian RuVs (2B) with that of global isolates and vaccine strain RA 27/3 (1a) revealed that the observed mutations in structural proteins have no major impact on the 3D structure, function and antigenicity. Indian RuVs formed three major clusters (Pune-1992, Kannur-2009 and Chitradurg-2007) in genome-based phylogeny of global isolates. Neutralizing antibody titers in a panel of serum samples from measles negative cases were significantly higher to the vaccine strain compared to a wild-type 2B isolate (Kannur) with concordance of 91.9%, thereby substantiating the use of current vaccines.


Asunto(s)
Virus de la Rubéola/genética , Virus de la Rubéola/inmunología , Rubéola (Sarampión Alemán) , Adulto , Anticuerpos Antivirales , Antígenos Virales , Niño , Femenino , Humanos , India/epidemiología , Embarazo , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control
4.
J Med Virol ; 92(10): 1932-1937, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32314811

RESUMEN

Coronavirus disease 2019 emerged as the first example of "Disease X", a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.


Asunto(s)
ARN Polimerasa Dependiente de ARN de Coronavirus/genética , Evolución Molecular , SARS-CoV-2/genética , Animales , Teorema de Bayes , Quirópteros/virología , Genética de Población , Humanos , Funciones de Verosimilitud , Pangolines/virología , Filogenia , Zoonosis/virología
5.
J Infect ; 80(3): 301-309, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31958542

RESUMEN

OBJECTIVE: To map genomic diversity of Measles virus (MeV) isolates collected during 2009-2017 from ten states of India. METHODS: Genome sequencing of Indian isolates and comparative genomics with global MeV using phylogeny, population stratification and selection pressure approaches were performed. RESULTS: The first report of complete genome sequences of forty-three Indian MeV isolates belonging to genotypes D4 (eight) and D8 (thirty-five). Three Indian isolates mapped to named strains D4-Enfield, D8-Villupuram and D8-Victoria. Indian D4 isolates deviate from standard genome length due to indels in M-F intergenic region. Estimated nucleotide substitution rates of Indian MeV derived using genome and individual genes are lower than that of global isolates. Phylogeny revealed genotype-based temporal clustering, suggesting existence of two lineages of D4 and three lineages of D8 in India. Absence of spatial clustering suggests role of cross-border travel in MeV transmission. CONCLUSIONS: Evolutionary analyses suggest the need for surveillance of MeV in India, particularly in view of diversified trajectories of D4 and D8 isolates. This study contributes to global measles epidemiology and indicates no major impact on antigenicity in Indian isolates, thereby substantiating the use of current vaccines to meet measles elimination target of 2023 set by World Health Organization for South-East Asia Region.


Asunto(s)
Virus del Sarampión , Sarampión , Genómica , Genotipo , Humanos , India/epidemiología , Sarampión/epidemiología , Virus del Sarampión/genética , Filogenia , Análisis de Secuencia de ADN
6.
Infect Genet Evol ; 49: 234-240, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28126562

RESUMEN

Dengue virus serotype 3 (DENV-3), one of the four serotypes of Dengue viruses, is geographically diverse. There are five distinct genotypes (I-V) of DENV-3. Emerging strains and lineages of DENV-3 are increasingly being reported. Availability of genomic data for DENV-3 strains provides opportunity to study its population structure. Complete genome sequences are available for 860 strains of four genotypes (I, II, III and V) isolated worldwide and were analyzed using population genetics and evolutionary approaches to map landscape of genomic diversity. DENV-3 population is observed to be stratified into five major subpopulations. Genotype I and II formed independent subpopulations while genotype III is subdivided into three subpopulations (GIII-a, GIII-b and GIII-c) and is therefore heterogeneous. Genotypes I, II and GIII-a subpopulations comprise of Asian strains whereas GIII-c comprises of American strains. GIII-b subpopulation includes mainly of American strains along with a few strains from Sri Lanka. Genetic admixture is predominantly observed in Sri Lankan strains of genotype III and all strains of genotype V. Inter-genotype recombination was observed to occur in non-structural region of several Asian strains whereas extent of recombination was limited in American strains. Significant positive selection was found to be operational on all genes and observed to be the main driving force of genetic diversity. Positive selection was strongly operational on the branches leading to Asian genotypes and helped to delineate the genetic differences between Asian and American lineages. Thus, inter-genotype recombination, migration and adaptive evolution are the major determinants of evolution of DENV-3.


Asunto(s)
Virus del Dengue/genética , Dengue/epidemiología , Genoma Viral , Genotipo , Filogenia , Serogrupo , Asia/epidemiología , Evolución Biológica , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Variación Genética , Humanos , Epidemiología Molecular , América del Norte/epidemiología , Filogeografía , Recombinación Genética , Selección Genética , América del Sur/epidemiología
7.
PeerJ ; 4: e2326, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27635316

RESUMEN

BACKGROUND: Dengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genus Flavivirus, family Flaviviridae). There are four serotypes of Dengue Virus (DENV-1 to DENV-4), each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics. DENV-2 consists of six genotypes such as Asian/American, Asian I, Asian II, Cosmopolitan, American and sylvatic. Comparative genomic study was carried out to infer population structure of DENV-2 and to analyze the role of evolutionary and spatiotemporal factors in emergence of diversifying lineages. METHODS: Complete genome sequences of 990 strains of DENV-2 were analyzed using Bayesian-based population genetics and phylogenetic approaches to infer genetically distinct lineages. The role of spatiotemporal factors, genetic recombination and selection pressure in the evolution of DENV-2 is examined using the sequence-based bioinformatics approaches. RESULTS: DENV-2 genetic structure is complex and consists of fifteen subpopulations/lineages. The Asian/American genotype is observed to be diversified into seven lineages. The Asian I, Cosmopolitan and sylvatic genotypes were found to be subdivided into two lineages, each. The populations of American and Asian II genotypes were observed to be homogeneous. Significant evidence of episodic positive selection was observed in all the genes, except NS4A. Positive selection operational on a few codons in envelope gene confers antigenic and lineage diversity in the American strains of Asian/American genotype. Selection on codons of non-structural genes was observed to impact diversification of lineages in Asian I, cosmopolitan and sylvatic genotypes. Evidence of intra/inter-genotype recombination was obtained and the uncertainty in classification of recombinant strains was resolved using the population genetics approach. DISCUSSION: Complete genome-based analysis revealed that the worldwide population of DENV-2 strains is subdivided into fifteen lineages. The population structure of DENV-2 is spatiotemporal and is shaped by episodic positive selection and recombination. Intra-genotype diversity was observed in four genotypes (Asian/American, Asian I, cosmopolitan and sylvatic). Episodic positive selection on envelope and non-structural genes translates into antigenic diversity and appears to be responsible for emergence of strains/lineages in DENV-2 genotypes. Understanding of the genotype diversity and emerging lineages will be useful to design strategies for epidemiological surveillance and vaccine design.

8.
Arch Virol ; 161(8): 2133-48, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27169727

RESUMEN

The spread of dengue disease has become a global public health concern. Dengue is caused by dengue virus, which is a mosquito-borne arbovirus of the genus Flavivirus, family Flaviviridae. There are four dengue virus serotypes (1-4), each of which is known to trigger mild to severe disease. Dengue virus serotype 4 (DENV-4) has four genotypes and is increasingly being reported to be re-emerging in various parts of the world. Therefore, the population structure and factors shaping the evolution of DENV-4 strains across the world were studied using genome-based population genetic, phylogenetic and selection pressure analysis methods. The population genomics study helped to reveal the spatiotemporal structure of the DENV-4 population and its primary division into two spatially distinct clusters: American and Asian. These spatial clusters show further time-dependent subdivisions within genotypes I and II. Thus, the DENV-4 population is observed to be stratified into eight genetically distinct lineages, two of which are formed by American strains and six of which are formed by Asian strains. Episodic positive selection was observed in the structural (E) and non-structural (NS2A and NS3) genes, which appears to be responsible for diversification of Asian lineages in general and that of modern lineages of genotype I and II in particular. In summary, the global DENV-4 population is stratified into eight genetically distinct lineages, in a spatiotemporal manner with limited recombination. The significant role of adaptive evolution in causing diversification of DENV-4 lineages is discussed. The evolution of DENV-4 appears to be governed by interplay between spatiotemporal distribution, episodic positive selection and intra/inter-genotype recombination.


Asunto(s)
Virus del Dengue/genética , Dengue/virología , Evolución Molecular , Genoma Viral , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Variación Genética , Genómica , Genotipo , Humanos , Filogenia , Proteínas Virales/genética , Proteínas Virales/metabolismo
9.
PLoS One ; 11(2): e0149350, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26870949

RESUMEN

Rhinoviruses (RV) are increasingly being reported to cause mild to severe infections of respiratory tract in humans. RV are antigenically the most diverse species of the genus Enterovirus and family Picornaviridae. There are three species of RV (RV-A, -B and -C), with 80, 32 and 55 serotypes/types, respectively. Antigenic variation is the main limiting factor for development of a cross-protective vaccine against RV.Serotyping of Rhinoviruses is carried out using cross-neutralization assays in cell culture. However, these assays become laborious and time-consuming for the large number of strains. Alternatively, serotyping of RV is carried out by alignment-based phylogeny of both protein and nucleotide sequences of VP1. However, serotyping of RV based on alignment-based phylogeny is a multi-step process, which needs to be repeated every time a new isolate is sequenced. In view of the growing need for serotyping of RV, an alignment-free method based on "return time distribution" (RTD) of amino acid residues in VP1 protein has been developed and implemented in the form of a web server titled RV-Typer. RV-Typer accepts nucleotide or protein sequences as an input and computes return times of di-peptides (k = 2) to assign serotypes. The RV-Typer performs with 100% sensitivity and specificity. It is significantly faster than alignment-based methods. The web server is available at http://bioinfo.net.in/RV-Typer/home.html.


Asunto(s)
Filogenia , Infecciones por Picornaviridae/virología , Rhinovirus/clasificación , Rhinovirus/genética , Serotipificación/métodos , Proteínas de la Cápside/genética , Genes Virales , Humanos , Internet , Programas Informáticos
10.
PLoS One ; 9(2): e88981, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24586469

RESUMEN

Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species. Although emerging lineages within Rhinoviruses have been reported, their population structure has not been studied yet. The availability of complete genome sequences facilitates study of population structure, genetic diversity and underlying evolutionary forces, such as mutation, recombination and selection pressure. Analysis of complete genomes of Rhinoviruses using a model-based population genetics approach provided a strong evidence for existence of seven genetically distinct subpopulations. As a result of diversification, Rhinovirus A and -C populations are divided into four and two subpopulations, respectively. Genetically, the Rhinovirus B population was found to be homogeneous. Intra-species recombination was observed to be prominent in Rhinovirus A and -C species. Significant evidence of episodic positive selection was obtained for several sites within coding sequences of structural and non-structural proteins. This corroborates well with known phenotypic properties such as antigenicity of structural proteins. Episodic positive selection appears to be responsible for emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus population is an ensemble of seven distinct lineages. In case of Rhinovirus A, intra-species recombination and episodic positive selection contribute to its further diversification. In case of Rhinovirus C, intra- and inter-species recombinations are responsible for observed diversity. Population genetics approach was further useful to analyze phylogenetic tree topologies pertaining to recombinant strains, especially when trees are derived using complete genomes. Understanding of population structure serves as a foundation for designing new vaccines and drugs as well as to explain emergence of drug resistance amongst subpopulations.


Asunto(s)
Evolución Molecular , Variación Genética , Rhinovirus/genética , Ligamiento Genético , Genoma Viral/genética , Humanos , Filogenia , ARN Viral/genética , Recombinación Genética , Infecciones del Sistema Respiratorio/virología , Rhinovirus/clasificación , Análisis de Secuencia de ARN
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