bioRxiv Science⌕ Search

Biology subjects

Venkat, V.

Publications and source records attributed to Venkat, V..

8 recordsLinked to original sources
bioRxiv2026

Detection and characterisation of alpha- and betacoronaviruses in rodents and bats from Germany, France, Belgium and Ireland

Recent zoonotic coronavirus outbreaks have sparked an interest in understanding coronaviruses circulating in animal reservoirs. While bats are recognised as major reservoirs for these viruses, coronaviruses have also been detected in a wide range of terrestrial small mammals, particularly rodents. However, coronavirus diversity in these mammals, specifically in Europe, is still poorly characterised. In this study, we detected and characterised coronaviruses in terrestrial small mammals and bats from Belgium, France, Germany, and Ireland. We screened tissue samples from rodents and shrews and environmental bat guano using pan-coronavirus real-time and conventional PCRs, with positive results confirmed by sanger sequencing. Among 2667 bat and 1152 terrestrial mammal samples, we detected 59 positive samples, 36 from bats and 23 from rodents, from which we recovered 60 coronavirus sequences, spanning both Alphacoronavirus and Betacoronavirus lineages. Through next generation sequencing we identified one Pipistrellus pygmaeus bat guano sample carrying two distinct alphacoronaviruses, representing Nyctacovirus and Pedacovirus subgenera. Among rodents, most coronavirus-positive samples originated from a zoo in Belgium, where several CoV lineages co-circulated. The identified rodent coronaviruses clustered among previously described rodent-associated lineages, some of which also include human and other mammal-derived coronavirus sequences. Consistent with previous studies, we found sarbecoviruses in horseshoe bats (particularly Rhinolophus ferrumequinum and R. hipposideros) and merbecoviruses in Plecotus auritus bats, and these viruses are distantly related to the human coronaviruses of the respective families. Similar to bat coronaviruses, some rodent coronaviruses strains seemed to be association with specific rodent species. In conclusion, our study enhances the understanding of coronaviruses in rodents and bats, revealing potential hotspots for these viruses and their implication for human and animal health. These findings underscore the necessity for continued surveillance of coronaviruses in wildlife reservoirs to mitigate future zoonotic spillover risks.

microbiology↗
bioRxiv2025

American mink as an animal model to study SARS-CoV-2 and vaccine response

Selecting a suitable animal model is crucial in understanding infectious diseases and developing vaccines. Here, we developed a receptor-binding domain -based SARS-CoV-2 vaccine with mouse Fc an immunopotentiator in a mink model. Four different variations of the vaccine were tested in groups of 30-31 American mink and followed for IgG and neutralizing antibodies (nAb) up to 27 weeks. Subcutaneous version induced a strong IgG and nAb response within two weeks and was still detectable at 27 weeks. Intranasal version also caused a detectable, although weaker, immune response. A simultaneously given subcutaneous vaccine against virus enteritis, botulism and hemorrhagic pneumonia potentially caused a lower SARS-CoV-2 antibody response, highlighting the need for further studies on co-effects of vaccines. In virus challenge with Alpha variant (B.1.1.7), vaccinated mink had a stronger antibody response than unvaccinated mink. Despite not preventing the infection, vaccinated mink had milder clinical signs and less virus in saliva. Another challenge of unvaccinated mink with Omicron variant showed similar results to alpha (BA.1) variant. Virus RNA was detected in the brain of unvaccinated mink but not vaccinated mink by in situ hybridization, indicating a suitability of mink to study neurological effects of SARS-CoV-2 and potentially long COVID as well. Author summaryFinding a good animal model is very important in studying infectious diseases and their treatment. The recent SARS-CoV2 pandemic highlighted this dilemma. We have developed an animal model based on mink due to their close match to humans in the symptomology of this disease. Such model will enable the study of relative susceptibility, transmission, tissue tropism, complex pathogenesis and long COVID, as well as prophylaxis and vaccines. This model will also help reduce the use of primates in this research. We have further developed a new vaccine for SARS-CoV2 based on the receptor binding domain of the S-protein with an inbuilt immune-enhancer. This vaccine underwent extensive testing in mink to determine response, long term protection, and safety. The vaccine was found to provide excellent titers of neutralizing antibodies with wide range in target variants. It also reduced the severity and duration of visible symptoms in the animals significantly. We propose this vaccine candidate for further study and future commercialization.

microbiology↗
bioRxiv2024

Disruptive changes in tissue microenvironment prime oncogenic processes at different stages of carcinogenesis in lung

Carcinogenesis is characterized not only by the uncontrolled growth of malignant cells but also by the disruption of the normal balance of cellular processes and intercellular interactions in the microenvironment that overcome the constraints of tissue homeostasis and support malignant growth. We profiled benign pulmonary dysplasia, carcinoma in situ, and invasive lung carcinomas at single-cell resolution to identify composite changes in cellular processes, signaling, and interactions among tumor-immune-stromal cells in the microenvironment in progressively advanced disease stages. We developed OncoTerrain, a hyperparameter-tuned model that captured synergistic multimodal signatures of an increasingly perturbed microenvironment in malignant disease stages and identified composite microenvironmental changes that supported cancer hallmarks. Key cancer-related changes in transcriptional states, cellular processes, and intercellular interactions involving immune, fibroblast, and stromal cell types preceded tumor initiation and were often synergistic. The microenvironment of increasingly malignant tissues was characterized by immune avoidance, ECM remodeling, and altered cell mobility. There were changes in cell states in fibroblasts, macrophages, and their inter-cellular interactions with other cell types, whereas T-cell activation occurred late. The in-situ carcinomas showed variations in the composite microenvironmental states that corroborated their pathology, which was not apparent at the genome level. A subset of those harbored populations of tumor and non-tumor cells with aggressive characteristics in some but not all aspects of hallmarks of carcinogenesis in the lung. We suspect that the variation in the coordination of microenvironmental cues may influence why some but not all in-situ tumors progress to the advanced stages.

genomics↗
bioRxiv2024

Deconstructing evolutionary histories of complex genomic rearrangements in lung malignancies

Somatic genomic rearrangements are hallmarks of cancer. Complex genomic rearrangements (CGRs) involving multiple intertwined structural alterations are often present in tumor genomes. CGRs frequently harbor oncogenic drivers, but their genomic architectures and etiologies are poorly understood. We used deep-coverage optical mapping technology to profile the genomic landscapes of normal lung tissues, benign pulmonary lesions, carcinoma in situ, and advanced carcinomas to examine the patterns of genome disorganization and instability in different stages of carcinogenesis in lung. Large rearrangements and CGRs were prevalent in the carcinomas. We developed omcplR to resolve the architecture of CGRs and predict their genesis from optical mapping data using genome-graph concept. We found that CGRs often arose from hierarchical combinations of multiple, localized simple structural variations, and harbored allelic heterogeneity at the affected loci. Rearrangement patterns and associated genomic signatures suggested that chromoanasynthesis was a likely prevalent mechanism driving complex genomic rearrangements. The early rearrangement junctions in intra-chromosomal CGRs were usually localized within the same chromatin domains, but the late junctions in advanced tumors had more heterogeneous contexts suggesting progressive organizational heterogeneity. The CGRs, especially the late events therein were under positive selection. A composite signature of genomic alterations including the CGRs captured the trajectory of progressive genomic disorganization and instability with carcinogenesis in lung and underscored the extent of genomic structural heterogeneity among the in-situ tumors.

genomics↗
bioRxiv2023

Evolution and Genetic Characterization of Seoul Virus in Wild Rats Rattus Norvegicus from an urban park in Lyon, France 2020-2022

Seoul virus (SEOV) is an orthohantavirus primarily carried by rats that can cause hemorrhagic fever with renal syndrome (HFRS) in humans. Nowaday s, its incidence is likely underestimated. We developed a comprehensive serological and molecular characterization of SEOV in Rattus norvegicus population from a popular urban park within a large city ( Park of La Tete dOr, Lyon, France) between 2020 and 2022. We confirmed the circulation of SEOV in rats from the park (seroprevalence 17.2%). The SEOV strains detected showed high genetic similar ity with the strain previously described in 2013 in this area. We found low structuring of wild rat populations within Lyon city. This study confirms the circulation of SEOV in Lyon city, in a park where opportunities for SEOV transmission to humans are numerous. Given the high gene flow between rat populations in the park and the rest of the city, we recommend conducting city-wide SEOV surveillance.

microbiology↗
bioRxiv2022

Serological surveillance for wild rodent infection with SARS-CoV-2 in Europe

We report serological surveillance for exposure to SARS-CoV-2 in 1,237 wild rodents and other small mammals across Europe. All samples were negative with the possible exception of one. Given the ongoing circulation of this virus in humans and potential host jumps, we suggest such surveillance be continued.

microbiology↗
bioRxiv2021

Lateral Preoptic Area Neurons Signal Cocaine Self-Administration Behaviors

The lateral preoptic area is implicated in numerous aspects of substance use disorder. In particular, the lateral preoptic area is highly sensitive to the pharmacological properties of psychomotor stimulants, and its activity promotes drug-seeking in the face of punishment and reinstatement during abstinence. Despite the lateral preoptic areas complicity in substance use disorder, how precisely lateral preoptic area neurons encode the individual components of drug self-administration has not been ascertained. To bridge this gap, we examined how the firing of single lateral preoptic area neurons correlates with three discrete elements of cocaine self-administration: 1) drug-seeking (pre-response), 2) drug-taking (response), and 3) receipt of the cocaine infusion. A significant subset of lateral preoptic area neurons responded to each component with a mix of increases and decreases in firing-rate. A majority of these neurons encoded the operant response with increases in spiking, though responses during the drug-seeking, taking, and reciept windows were highly correlated.

neuroscience↗