Biology subjects

Kumar, S.

Publications and source records attributed to Kumar, S..

At least 379 records · Page 21Linked to original sources

bioRxiv2022

Focal adhesion assembly requires phosphorylation signaling

Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) substrate Cas (Crk-associated substrate, p130Cas, BCAR1) is phosphorylated, and associated with its effectors, Crk/CrkL, in clusters that are precursors of focal adhesions. The initial phospho-Cas clusters contain integrin {beta}1 in its inactive, bent closed, conformation. Later, phospho-Cas and total Cas levels decrease as integrin {beta}1 is activated and core focal adhesion proteins including vinculin, talin, kindlin and paxillin are recruited. Cas is required for cell spreading and focal adhesion assembly in epithelial and fibroblast cells on collagen and fibronectin. Cas cluster formation requires Cas, Crk/CrkL, SFKs and Rac1 but not vinculin. Rac1 provides positive feedback onto Cas through reactive oxygen, opposed by negative feedback from the ubiquitin proteasome system. The results suggest a two-step model for focal adhesion assembly in which clusters of phospho-Cas, effectors and inactive integrin {beta}1 grow through positive feedback prior to integrin activation and recruitment of core focal adhesion proteins.

cell biology↗

bioRxiv2022

Long COVID: G Protein-Coupled Receptors (GPCRs) responsible for persistent post-COVID symptoms

As of early December 2022, COVID-19 had a significant impact on the lives of people all around the world, with over 630 million documented cases and over 6 million deaths. A recent clinical analysis revealed that under certain conditions, a patients disease symptoms are more likely to persist. Long COVID is characterised by many symptoms that continue long after the SARS-CoV-2 infection has resolved. This work utilised computational methods to analyse the persistence of COVID symptoms after recovery and to identify the relevant genes. Based on functional similarity, differentially expressed genes (DEGs) of SARS-CoV-2 infection and 255 symptoms of long covid were examined, and potential genes were identified based on the rank of functional similarity. Then, hub genes were identified by analysing the interactions between proteins. Using the identified key genes and the drug-gene interaction score, FDA drugs with potential for possible alternatives were identified. Also discovered were the gene ontology and pathways for 255 distinct symptoms. A website (https://longcovid.omicstutorials.com/) with a list of significant genes identified as biomarkers and potential treatments for each symptom was created. All of the hub genes associated with the symptoms, GNGT1, GNG12, GNB3, GNB4, GNG13, GNG8, GNG3, GNG7, GNG10, and GNAI1, were discovered to be associated with G-protein coupled receptors. This demonstrates that persistent COVID infection affects various organ systems and promotes chronic inflammation following infection. CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1 were identified as the common genes that regulate T-cell immunity via GPCR and cause a variety of symptoms, including autoimmunity, cardiovascular, dermatological, general symptoms, gastrointestinal, pulmonary, reproductive, genitourinary, and endocrine symptoms (RGEM). Among other functions, they were found to be involved in the positive regulation of protein localization to the cell cortex, the regulation of triglyceride metabolism, the binding of G protein-coupled receptors, the binding of G protein-coupled serotonin receptors, the heterotrimeric G-protein complex, and the cell cortex region. These biomarker data, together with the gene ontology and pathway information that accompanies them, are intended to aid in determining the cause and improving the efficacy of treatment.

bioinformatics↗

bioRxiv2022

Novel Peptide Inhibitor of Human Tumor Necrosis Factor-α has Antiarthritic Activity

The inhibition of tumor necrosis factor- (TNF) trimer formation renders it inactive for binding to its receptors thus mitigating the vicious cycle of inflammation. We designed a peptide (PIYLGGVFQ) that simulates a sequence strand of human TNF monomer using a series of in silico methods, such as active site finding (Acsite), protein-protein interaction (PPI), docking studies (GOLD and Modeller) followed by molecular dynamics (MD) simulation studies. The MD studies confirmed the intermolecular interaction of the peptide with the TNF. Fluorescence-activated cell sorting (FACS) and fluorescence microscopy revealed that the peptide effectively inhibited the binding of TNF to the cell surface receptors. The cell culture assays showed that the peptide significantly inhibited the TNF-mediated cell death. In addition, the nuclear translocation of the nuclear factor kappa B (NF{kappa}B) was significantly suppressed in the peptide-treated A549 cells as observed in immunofluorescence and gel mobility-shift assays. Furthermore, peptide protected against joint damage in collagen-induced arthritis (CIA) mouse model as revealed in the microfocal-CT scans. In conclusion, this TNF antagonist would be useful for the prevention and repair of inflammatory bone destruction and subsequent loss in the mouse model of CIA as well as human rheumatoid arthritis (RA) patients. This calls upon further clinical investigation to utilize its potential effect as an anti-arthritic drug.

immunology↗

bioRxiv2022

Evaluation of the safety, immunogenicity and efficacy of a new live-attenuated lumpy skin disease vaccine in India

Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed using an Indian field strain (LSDV/India/2019/Ranchi). The virus was attenuated by continuous passage (P=50) in Vero cells. The vaccine (50th LSDV passage in Vero cells, named as Lumpi-ProVacInd) did not induce any local or systemic reaction upon its experimental inoculation in calves (n=10). At day 30 post-vaccination (pv), the vaccinated animals were shown to develop antibody- and cell-mediated immune response and exhibited complete protection upon virulent LSDV challenge. We observed a minimum Neethling response (0.018% animals; 5 out of 26940 animals) of the vaccine in field trials among 26940 animals. There was no significant reduction in the milk yield in lactating animals (n=10108), besides there was no abortion or any other reproductive disorder in the pregnant animals (n=2889). Sero-conversion was observed in 85.18% animals in the field by day 30 pv.

microbiology↗

bioRxiv2022

BCLncRDB: A comprehensive database of LncRNAs associated with breast cancer

MotivationBreast cancer, the most common cancer in women, is characterized by high morbidity and mortality worldwide. Recent evidence has shown that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of breast cancer. Despite this, no database exists primarily for lncRNAs associated with only breast cancer. ResultsWe developed BCLncRDB, a manually curated, comprehensive database of lncRNAs associated with breast cancer. For this, we collected, processed, and analyzed data on breast cancer-associated lncRNAs from different sources, including published literature and TCGA. Currently, our database contains 5,279 unique breast cancer-lncRNA associations. It has the following features: (I) Differentially expressed and methylated lncRNAs, (II) Stage and subtype-specific lncRNAs, and (III) Drugs, Subcellular localization, Sequence, and Chromosome information. Thus, the BCLncRDB provides a dedicated platform for exploring breast cancer-related lncRNAs to advance and support the ongoing research on this disease. Availability and implementationThe database BCLncRDB is publicly available for use at http://sls.uohyd.ac.in/new/bclncrdb. Contactvaibhav@uohyd.ac.in

bioinformatics↗

bioRxiv2022

Differential roles of extracellular matrix proteins on primary and metastatic pancreatic cancer cells

Pancreatic cancer adenocarcinoma (PDAC) is reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma, which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and non-malignant cells such as inflammatory cells, cancer-associated fibroblasts, and lymphatic and blood vessels. Here, we decoupled the effects of the ECM on PDAC cell lines by culturing cells on surfaces coated with different ECM proteins. Our data show that the primary tumor-derived cell lines have different morphology depending on the ECM proteins on which they are cultured, while metastatic lesion-derived PDAC lines morphology does not change with respect to the different ECM proteins. Similarly, ECM proteins modulate the proliferation rate and the gemcitabine sensitivity of the primary tumor PDAC cell lines, but not the metastatic PDAC lines. Lastly, transcriptomics analysis of the primary tumor PDAC cells cultured on different ECM proteins reveals the regulation of various pathways, such as cell cycle, cell adhesion molecules, and focal adhesion, including the regulation of several integrin genes that are essential for ECM recognition.

cancer biology↗

bioRxiv2022

Genomic variations drive phenotypic heterogeneity in pancreatic cancer cells

ObjectivesTo evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells phenotypic, genomic, and transcriptomic heterogeneity. MethodsMIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively. ResultsFour MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones. ConclusionsMIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.

cancer biology↗

bioRxiv2022

Optogenetic closed-loop feedback control of the unfolded protein response optimizes protein production

In biotechnological protein production processes, the onset of protein unfolding at high gene expression levels leads to diminishing production yields and reduced efficiency. Here we show that in silico closed-loop optogenetic feedback control of the unfolded protein response (UPR) clamps gene expression rates at intermediate near-optimal values, leading to significantly improved product titers. Specifically, in a fully-automated custom-built 1L-photobioreactor, we used a cybergenetic control system to steer the level of UPR in yeast to a desired set-point by optogenetically modulating the expression of a hard-to-fold protein based on real-time feedback measurements of the UPR, resulting in 60% higher product titers. This proof-of-concept study paves the way for advanced optimal biotechnology production strategies that diverge from and complement current strategies employing constitutive overexpression or genetically hardwired circuits.

bioengineering↗

bioRxiv2022

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response

A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.

immunology↗

bioRxiv2022

Single and multi-analyte deep learning-based analysis framework for class prediction in biological images

Measurement of biological analytes, characterizing flavor in fruits, is a cumbersome, expensive and time-consuming process. Fruits with higher concentration of analytes have greater commercial or nutritional values. Here, we tested a deep learning-based framework with fruit images to predict the class (sweet or sour and high or low) of analytes using images from two types of trees in a single and multi-analyte mode. We used fruit images from kinnow (n = 3,451), an edible hybrid mandarin and neem (n = 1,045), a tree with agrochemical and pharmaceutical properties. We measured sweetness in kinnows and five secondary metabolites in neem fruits (azadirachtin or A, deacetyl-salannin or D, salannin or S, nimbin or N and nimbolide or E) using a refractometer and high-performance liquid chromatography, respectively. We trained the models for 300 epochs, before and after hyper-parameters evolution, using 300 generations with 50 epochs/generation, estimated the best models and evaluated their performance on 10% of independent images. The validation F1score and test accuracies were 0.79 and 0.77, and 82.55% and 60.8%, respectively for kinnow and neem A analyte. A multi-analyte model enhanced the neem A models prediction to high class when the D:N:Ss combined class predictions were high:low:high and to low class when D:Ns combined class predictions were low:high respectively. The test accuracy increased further to ~70% with a 10-fold cross-validation error of 0.257 across ten randomly split train:validation:test sets proving the potential of a multi-analyte model to enhance the prediction accuracy, especially when the numbers of images are limiting.

plant biology↗

bioRxiv2022

Architecture and topologies of gene regulatory networks associated with breast cancer, adjacent normal, and normal tissues

Most cancer studies employ adjacent normal tissues to tumors (ANTs) as controls, which are not completely normal and represent a pre-cancerous state. However, the regulatory landscape of ANTs and how it differs from tumor and non-tumor-bearing normal tissues is largely unexplored. Among cancers, breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide, with a lack of sufficient treatment regimens due to various reasons. Hence, we aimed to gain deeper insights into normal, pre-cancerous, and cancerous regulatory systems of the breast tissues towards the identification of ANT and subtype-specific candidate genes. For this, we constructed and analyzed eight gene regulatory networks (GRNs), including five different subtypes (viz. Basal, Her2, LuminalA, LuminalB, and Normal-Like), one ANT, and two normal tissue networks. Whereas several topological properties of these GRNs enabled us to identify tumor-related features of ANT; escape velocity centrality (EVC+) identified 24 functionally significant common genes, including well-known genes such as E2F1, FOXA1, JUN, BRCA1, GATA3, ERBB2, and ERBB3 across different subtypes and ANT. Similarly, the EVC+ also helped us to identify tissue-specific key genes (Basal: 18, Her2: 6, LuminalA: 5, LuminalB: 5, Normal-Like: 2, and ANT: 7). Additionally, differential correlation along with functional, pathway, and disease annotations highlighted the cancer-associated role of these genes. In a nutshell, the present study revealed ANT and subtype-specific regulatory features and key candidate genes which can be explored further using in vitro and in vivo experiments for better and effective disease management at an early stage.

bioinformatics↗

bioRxiv2022

Newcastle disease virus elevates its replication by instigating oxidative stress-driven Sirtuin 7 production

Reactive oxygen species (ROS) accumulation inside the cells instigates oxidative stress leading to the activation of stress-responsive genes. The persistence of stress halts the cells antiviral response, from which numerous viruses benefit. The viral strategies for promoting stressful conditions and utilizing the induced host proteins to enhance their replication remain elusive. The present work investigates the impact of oxidative stress on NDV pathogenesis. Here, we report that the progression of NDV infection depends on intracellular ROS production. Additionally, the results demonstrate the elevation of SIRT7 levels at transcription and translational levels post-NDV infection, which in turn is associated with the positive regulation of cellular protein deacetylation. A detailed mechanistic study in vitro and in ovo was also carried out utilizing SIRT7 activity modulators to decipher the underlying role in infection, either constructive or destructive. Lastly, we concluded that the elevated expression of NDV-mediated SIRT7 protein with an enhanced activity metabolizes the NAD+ to deacetylase the host proteins, thus contributing to high virus replication. ImportanceAlthough the instigation of oxidative stress during NDV infection has been reported several times, the cellular stress-responsive proteins direct function in virus replication is yet to be well understood. This study highlights the plausible stress-responsive proteins involved in viral pathogenesis while exploring the detailed molecular mechanisms of crosstalk between the activated cellular protein and the progress of the NDV replication cycle. Moreover, previous studies describing how different viruses modulate cellular stress may not fully reflect the complete picture of viral strategies. Here, we demonstrate NDV-influenced active involvement of SIRT7 activity leading to the deacetylation of host proteins. It helped us better understand the viruss strategies to generate its numerous copies while perturbing the host cells standard functionality and opening up new possibilities for infection interventions.

microbiology↗

bioRxiv2022

Enrichment of phenotype among biological forms of Anopheles stephensi Liston through establishment of isofemale lines

The success of vector management programs relies on knowledge of the biology and genetic make-up of mosquitoes so that they can be interlaced with modern tools for developing suitable intervention strategies. There are many reports available for rearing varied species of mosquito vectors. However, there are limited studies addressing the development of isofemale lines among mosquitoes to homogenize the population to obtain both high-quality genome assemblies and enrichment of phenotype. Anopheles stephensi, an urban malaria vector, is one of the major invasive vectors of malaria distributed throughout the Indian subcontinent, Middle East, and has recently been expanding its range in Africa. With the existence of three biological forms, distinctly identifiable based on the number of ridges on eggs with varying vectorial competence, An. stephensi is a perfect species for developing a method for the successful establishment of isofemale lines, which can be tested for retention of the expected vectorial competence for the various forms. We describe the key steps in the establishment and validation of isofemale lines, which include monitoring the transgenerational fitness traits, morphometrics of eggs, and adult wing size during every generation. After the initial inbreeding depression, as proof of the tedious selection process, no significant morphometric differences were observed in the wings and egg size between the parental and their respective isofemale lines. We observed a significant change in the vectorial competence between the respective isofemale and parental lines enriching expected differential susceptibility towards malaria parasites by the type and intermediate forms. Interestingly, IndCh and IndInt strains showed variations in resistance to different insecticides belonging to all the four major classes. These variant lines have been characterized for their levels of homozygosity both at the phenotype and genotype levels and can be used as a standard reference or as a biological resource for other studies related to urban malaria research. Author summaryIsofemale lines can be a valuable resource for characterizing and enhancing several genotypic and phenotypic traits. This is the first detailed report of the establishment of two isofemale lines of type and intermediate biological forms in Anopheles stephensi. The work encompasses the characterization of fitness traits among the two lines through a transgenerational study. Further, isofemale colonies were established and used to characterize insecticide susceptibility and vector competence. The study provides valuable insights into the differential susceptibility status of the parental and isofemale to different insecticides belonging to the same class. Corroborating with the earlier hypothesis we exemplify the high vector competence in type form than the intermediate from using homozygous isofemale lines. Using these isofemale lines it is now possible to study host-parasite interactions and identify factors that might be responsible for altered susceptibility and increased vector competence in An. stephensi biological forms that would also pave way for developing better vector management strategies.

genetics↗

bioRxiv2022

Deep phylotaxonogenomic revision of the genus Xanthomonas within family Xanthomonadaceae and proposal of novel family Frateuriaceae within order Xanthomonadales

Genus Xanthomonas is primarily comprise phytopathogenic species. In a recent study by carrying out deep phyto-taxonogenomics, we reported that even the genera Xylella, Stenotrophomonas and Pseudoxanthomonas are miss-classified and belong to genus Xanthomonas. Hence to understand the breadth of the genus, we carried out deep phylo-taxonogenomics of the order Xanthomonadales. Such investigation revealed that at least four more genera belong to genus Xanthomonas with prominent being Lysobacter. Further order level deep phylo-taxonogenomics revealed two major families. One being the original family Xanthomonadaceae and other is proposed as Frateuriaceae fam. nov. as synonym of family Rhodanobacteraceae with novel genus Frateuria gen. nov.

microbiology↗

bioRxiv2022

Loss of estrogen unleashing neuro-inflammation increases the risk of Alzheimer's disease in women

The risk of Alzheimers disease (AD) in women is about 2 times greater than in men. The estrogen hypothesis is being accepted as the essential sex factor causing the sex difference in AD. Also, the recent meta-analysis using large-scale medical records data indicated estrogen replacement therapy. However, the underlying molecular targets and mechanisms explaining this sex difference in AD disease development remain unclear. In this study, we identified that estrogen treatment can strongly inhibition of neuro-inflammation signaling targets, using the systems pharmacology model; and identified ESR1/ESR2 (the receptors of estrogen) are topologically close to the neuroinflammation biomarker genes using signaling network analysis. Moreover, the estrogen level in women decreased to an extremely lower level than in men after age 55. Pooling together the multiple pieces of evidence, it is concluded that the loss of estrogen unleashing neuro-inflammation increases the womens risk of Alzheimers disease. These analysis results provide novel supporting evidence explaining the potential mechanism of the anti-neuroinflammation role of estrogen causing the sex difference of AD. Medications boosting the direct downstream signaling of ESR1/ESR2, or inhibiting upstream signaling targets of neuroinflammation, like JAK2 inhibitors, on the signaling network can be potentially effective or synergistic combined with estrogen for AD prevention and treatment.

neuroscience↗

bioRxiv2022

Optogenetic Instruction of Cell Fate by Temporal Patterning of Mechanobiological Signals

During the intricate process by which cells give rise to tissues, embryonic and adult stem cells are exposed to diverse mechanical signals from the extracellular matrix (ECM) that influence their fate. Cells can sense these cues in part through dynamic generation of protrusions, modulated and controlled by cyclic activation of Rho GTPases. However, it remains unclear how extracellular mechanical signals regulate Rho GTPase activation dynamics and how such rapid, transient activation dynamics are integrated to yield long-term, irreversible cell fate decisions. Here, we report that ECM stiffness cues alter not only the magnitude but also the temporal frequency of RhoA and Cdc42 activation in adult neural stem cells (NSCs). Using optogenetics to control the frequency of RhoA and Cdc42 activation, we further demonstrate that these dynamics are functionally significant, where high- or low-frequency activation of RhoA and Cdc42 drives astrocytic or neuronal differentiation, respectively. In addition, high-frequency Rho GTPase activation induces sustained phosphorylation of the TGF{beta} pathway effector SMAD1, which in turn promotes astrocytic differentiation. By contrast, under low-frequency Rho GTPase stimulation, cells fail to accumulate SMAD1 phosphorylation and undergo neurogenesis. Our findings reveal the temporal patterning of Rho GTPase signaling and the resulting accumulation of a SMAD1 signal as a critical mechanism through which ECM stiffness cues regulate NSC fate.

cancer biology↗

bioRxiv2022

Cellular Heterogeneity of Pluripotent Stem Cell Derived Cardiomyocyte Grafts is Mechanistically Linked to Treatable Arrhythmias

BackgroundExciting pre-clinical data have confirmed that human pluripotent stem cell derived cardiomyocytes (PSC-CMs) can remuscularise the injured or diseased heart, with several clinical trials now in planning or recruitment stages worldwide. However, ventricular arrhythmias are a predictable complication following engraftment of intramyocardially injected PSC-CMs. Therefore, there is an urgent unmet need to gain mechanistic insights and treatment strategies to control or prevent these engraftment arrhythmias (EAs). MethodsWe used a porcine model of myocardial infarction and PSC-CM transplantation to investigate efficacy of pharmacologic and catheter based anti-arrhythmic strategies in mitigating EAs. Furthermore, cell doses were robustly phenotyped using single cell ribonucleic acid sequencing and high parameter flow cytometry to identify cellular characteristics predictive of arrhythmogenesis. ResultsCombination therapy with amiodarone and ivabradine significantly reduced EA rate and burden following PSC-CM transplantation. Catheter ablation was also a feasible and effective treatment strategy which could be considered in the case of pharmacologically refractory arrhythmias. In addition, we show that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. We further describe two unique surface marker signatures, SIRPA+/CD90-/CD200+ and SIRPA+/CD90-/CD200-, which identify arrhythmogenic and non-arrhythmogenic cardiomyocytes respectively. ConclusionOur data deepens mechanistic understanding of EAs and suggests that modifications to current PSC-CM production and/or selection protocols could ameliorate this problem. We further show that current clinical pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias, an important safety consideration given several impending clinical trials.

cell biology↗

bioRxiv2022

Genome characterization of monkeypox cases detected in India: Identification of three sub clusters among A.2 lineage

Since May 2022, Monkeypox, a zoonotic Orthopox DNA virus was reported in more than 102 countries indicating expansion of its geographic range. We analyzed the complete genomes sequences of Monkeypox cases from Kerala (n=5 travelled from UAE) and Delhi (n=5 no travel history), India confirmed during July to August 2022. All the retrieved MPXV sequences from India covering 90 to 99% genome belong to A.2 lineage of clade IIb. The A.2 MPXV lineage divided in three sub clusters; first cluster Kerala n=5, Delhi n=2 aligned with the USA-2022 ON674051.1; while second of Delhi n=3 aligned with USA-2022 ON675438.1 and third consists of the UK, USA and Thailand. Recent update in MPXV lineage designated all the five sequences from Kerala as A.2.1. In addition to known 16 single nucleotide polymorphisms (SNPs) along with 13 APOBEC3 cytosine deaminase activity determined specific lineage defining mutations in A.2 lineage, 25 additional APOBEC3 mutations were found in 10 reported sequences. The study emphasizes need of enhancing genomic surveillance to understand the mutation and its linkage.

microbiology↗