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Article ; Online: Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases.

Vaidya, Sunil R / Kumbhar, Neelakshi S / Andhare, Gargi K / Pawar, Nilesh / Walimbe, Atul M / Kinikar, Meenal / Kasibhatla, Sunitha M / Kulkarni-Kale, Urmila

Viruses

2023 Volume 15, Issue 11

Abstract: The neutralizing antibody (Nt-Ab) response to vaccine and wild-type measles viruses (MeV) was studied in suspected measles cases reported during the years 2012-2016. The neutralization activity against MeV A, D4 and D8 genotypes was studied on sera ( ... ...

Abstract	The neutralizing antibody (Nt-Ab) response to vaccine and wild-type measles viruses (MeV) was studied in suspected measles cases reported during the years 2012-2016. The neutralization activity against MeV A, D4 and D8 genotypes was studied on sera (Panel A; n = 68 (measles-immunized) and Panel B; n = 50 (unvaccinated)) that were either laboratory confirmed or not confirmed by the presence of IgM antibodies. Additionally, the Nt-Ab response in Panel A was measured against the MeV vaccine and four wild-type viruses. Neutralization results were compared using homology modeling and molecular dynamics simulation (MDS) of MeV-hemagglutinin (H) and fusion (F) proteins. Overall, the Nt-Ab titres for MeV-A were found to be significantly lower than MeV-D4 and MeV-D8 viruses for Panel A. No major difference was noted in Nt-Ab titres between MeV-D8 viruses (Jamnagar and New Delhi), whereas MeV-D4 (Sindhudurg and Bagalkot (BGK) viruses) showed significant differences between Nt-Ab titres for Panel B. Interestingly, the substitutions observed in epitopes of H-protein, L249P and G316A are observed to be unique to MeV-BGK. MDS of H-protein revealed significant fluctuations in neutralizing epitopes due to L249P substitution. The majority of the clinically suspected cases showed Nt-Abs to MeV wild-types. Higher IgG antibody avidity and Nt-Ab titres were noted in IgM-negatives than in IgM-positives cases, indicating reinfection or breakthrough. MDS revealed reduced neutralization due to decreased conformational flexibility in the H-epitope.
MeSH term(s)	Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Neutralization Tests ; Measles virus/genetics ; Measles ; Measles Vaccine ; Epitopes ; Immunoglobulin M
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Measles Vaccine ; Epitopes ; Immunoglobulin M
Language	English
Publishing date	2023-11-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15112243
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Article ; Online: Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak.

Limaye, Sanket / Kasibhatla, Sunitha M / Ramtirthkar, Mukund / Kinikar, Meenal / Kale, Mohan M / Kulkarni-Kale, Urmila

Viruses

2021 Volume 13, Issue 11

Abstract: 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. ...

Abstract	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.
MeSH term(s)	COVID-19/epidemiology ; COVID-19/virology ; Evolution, Molecular ; Genome, Viral ; Humans ; India/epidemiology ; Models, Molecular ; Mutation ; Phylogeny ; Protein Conformation ; Protein Domains ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Selection, Genetic ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Whole Genome Sequencing
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-11-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112238
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Article: Circulation and Evolution of SARS-CoV-2 in India: Let the Data Speak

Limaye, Sanket / Kasibhatla, Sunitha M. / Ramtirthkar, Mukund / Kinikar, Meenal / Kale, Mohan M. / Kulkarni-Kale, Urmila

Viruses. 2021 Nov. 08, v. 13, no. 11

2021

Abstract	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.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; genome ; genomics ; glycosylation ; immune evasion ; monitoring ; monophyly ; neutralization ; pandemic ; population genetics ; trees ; India
Language	English
Dates of publication	2021-1108
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112238
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene.

Kasibhatla, Sunitha M / Kinikar, Meenal / Limaye, Sanket / Kale, Mohan M / Kulkarni-Kale, Urmila

Journal of medical virology

2020 Volume 92, Issue 10, Page(s) 1932–1937

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Bayes Theorem ; Chiroptera/virology ; Coronavirus RNA-Dependent RNA Polymerase/genetics ; Evolution, Molecular ; Genetics, Population ; Humans ; Likelihood Functions ; Pangolins/virology ; Phylogeny ; SARS-CoV-2/genetics ; Zoonoses/virology
Chemical Substances	Coronavirus RNA-Dependent RNA Polymerase (EC 2.7.7.48)
Keywords	covid19
Language	English
Publishing date	2020-06-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25909
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Article ; Online: Characterization of diversity of measles viruses in India: Genomic sequencing and comparative genomics studies.

Vaidya, Sunil R / Kasibhatla, Sunitha M / Bhattad, Divya R / Ramtirthkar, Mukund R / Kale, Mohan M / Raut, Chandrashekhar G / Kulkarni-Kale, Urmila

The Journal of infection

2020 Volume 80, Issue 3, Page(s) 301–309

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Genomics ; Genotype ; Humans ; India/epidemiology ; Measles/epidemiology ; Measles virus/genetics ; Phylogeny ; Sequence Analysis, DNA
Language	English
Publishing date	2020-01-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2019.11.025
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Article: Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene

Kasibhatla, Sunitha M / Kinikar, Meenal / Limaye, Sanket / Kale, Mohan M / Kulkarni-Kale, Urmila

J. med. virol

Abstract	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.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #96737
Database	COVID19

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Article ; Online: Understanding evolution of SARS‐CoV‐2

Kasibhatla, Sunitha M. / Kinikar, Meenal / Limaye, Sanket / Kale, Mohan M. / Kulkarni‐Kale, Urmila

Journal of Medical Virology

A perspective from analysis of genetic diversity of RdRp gene

2020 Volume 92, Issue 10, Page(s) 1932–1937

Keywords	Virology ; Infectious Diseases ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25909
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Article ; Online: Genetic and antigenic characterization of wild type rubella viruses isolated from India.

Vaidya, Sunil R / Kasibhatla, Sunitha M / Kamble, Madhukar B / Munivenkatappa, Ashok / Kumbhar, Neelakshi S / Jayaswamy, Manjunatha M / Ramtirthkar, Mukund R / Kale, Mohan M / Kulkarni-Kale, Urmila

Vaccine

2021 Volume 39, Issue 6, Page(s) 876–881

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Adult ; Antibodies, Viral ; Antigens, Viral ; Child ; Female ; Humans ; India/epidemiology ; Pregnancy ; Rubella/epidemiology ; Rubella/prevention & control ; Rubella virus/genetics ; Rubella virus/immunology
Chemical Substances	Antibodies, Viral ; Antigens, Viral
Language	English
Publishing date	2021-01-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2020.12.063
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Article ; Online: Chickpea-Fusarium oxysporum interaction transcriptome reveals differential modulation of plant defense strategies.

Upasani, Medha L / Limaye, Bhakti M / Gurjar, Gayatri S / Kasibhatla, Sunitha M / Joshi, Rajendra R / Kadoo, Narendra Y / Gupta, Vidya S

Scientific reports

2017 Volume 7, Issue 1, Page(s) 7746

Abstract: Fusarium wilt is one of the major biotic stresses reducing chickpea productivity. The use of wilt-resistant cultivars is the most appropriate means to combat the disease and secure productivity. As a step towards understanding the molecular basis of wilt ...

Abstract	Fusarium wilt is one of the major biotic stresses reducing chickpea productivity. The use of wilt-resistant cultivars is the most appropriate means to combat the disease and secure productivity. As a step towards understanding the molecular basis of wilt resistance in chickpea, we investigated the transcriptomes of wilt-susceptible and wilt-resistant cultivars under both Fusarium oxysporum f.sp. ciceri (Foc) challenged and unchallenged conditions. Transcriptome profiling using LongSAGE provided a valuable insight into the molecular interactions between chickpea and Foc, which revealed several known as well as novel genes with differential or unique expression patterns in chickpea contributing to lignification, hormonal homeostasis, plant defense signaling, ROS homeostasis, R-gene mediated defense, etc. Similarly, several Foc genes characteristically required for survival and growth of the pathogen were expressed only in the susceptible cultivar with null expression of most of these genes in the resistant cultivar. This study provides a rich resource for functional characterization of the genes involved in resistance mechanism and their use in breeding for sustainable wilt-resistance. Additionally, it provides pathogen targets facilitating the development of novel control strategies.
MeSH term(s)	Cicer/genetics ; Cicer/immunology ; Cicer/microbiology ; Fusarium/pathogenicity ; Genes, Plant ; Host-Pathogen Interactions ; Plant Immunity ; Transcriptome
Language	English
Publishing date	2017-08-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-07114-x
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Article ; Online: Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle.

Mendum, Tom A / Chandran, Aneesh / Williams, Kerstin / Vordermeier, H Martin / Villarreal-Ramos, Bernardo / Wu, H / Singh, Albel / Smith, Alex A / Butler, Rachel E / Prasad, Aravind / Bharti, Neeraj / Banerjee, Ruma / Kasibhatla, Sunitha M / Bhatt, Apoorva / Stewart, Graham R / McFadden, Johnjoe

BMC genomics

2019 Volume 20, Issue 1, Page(s) 431

Abstract: Background: BCG is the most widely used vaccine of all time and remains the only licensed vaccine for use against tuberculosis in humans. BCG also protects other species such as cattle against tuberculosis, but due to its incompatibility with current ... ...

Abstract	Background: BCG is the most widely used vaccine of all time and remains the only licensed vaccine for use against tuberculosis in humans. BCG also protects other species such as cattle against tuberculosis, but due to its incompatibility with current tuberculin testing regimens remains unlicensed. BCG's efficacy relates to its ability to persist in the host for weeks, months or even years after vaccination. It is unclear to what degree this ability to resist the host's immune system is maintained by a dynamic interaction between the vaccine strain and its host as is the case for pathogenic mycobacteria. Results: To investigate this question, we constructed transposon mutant libraries in both BCG Pasteur and BCG Danish strains and inoculated them into bovine lymph nodes. Cattle are well suited to such an assay, as they are naturally susceptible to tuberculosis and are one of the few animal species for which a BCG vaccination program has been proposed. After three weeks, the BCG were recovered and the input and output libraries compared to identify mutants with in vivo fitness defects. Less than 10% of the mutated genes were identified as affecting in vivo fitness, they included genes encoding known mycobacterial virulence functions such as mycobactin synthesis, sugar transport, reductive sulphate assimilation, PDIM synthesis and cholesterol metabolism. Many other attenuating genes had not previously been recognised as having a virulence phenotype. To test these genes, we generated and characterised three knockout mutants that were predicted by transposon mutagenesis to be attenuating in vivo: pyruvate carboxylase, a hypothetical protein (BCG_1063), and a putative cyclopropane-fatty-acyl-phospholipid synthase. The knockout strains survived as well as wild type during in vitro culture and in bovine macrophages, yet demonstrated marked attenuation during passage in bovine lymph nodes confirming that they were indeed involved in persistence of BCG in the host. Conclusion: These data show that BCG is far from passive during its interaction with the host, rather it continues to employ its remaining virulence factors, to interact with the host's innate immune system to allow it to persist, a property that is important for its protective efficacy.
MeSH term(s)	Animals ; BCG Vaccine ; Cattle ; Cholesterol/metabolism ; DNA Transposable Elements ; Gene Library ; Genes, Bacterial ; Genetic Fitness ; Mycobacterium bovis/genetics ; Mycobacterium bovis/metabolism ; Oxazoles ; Sugars/metabolism ; Sulfates/metabolism ; Tuberculosis, Bovine/microbiology
Chemical Substances	BCG Vaccine ; DNA Transposable Elements ; Oxazoles ; Sugars ; Sulfates ; mycobactins ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2019-05-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-019-5791-1
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