Interaction of viruses with the host is fundamental to initiate an infection, and to complete a successful virus replication cycle. However, the outcome of this initiation depends up several factors of both virus and host origins. Among host responses, the most profound host-comeback is the induction of innate immune responses, mediated by the central players, interferon (IFN) signalling molecules.
The induction of IFNs is generic but the terminal actions can be host and pathogen specific, and is primarily contributed by the IFN-stimulated or virus-regulated proteins. In this context, the chicken is unique since even in the updated version of the chicken genome, it appears that chicken lack crucial elements in IFN-induction and signalling pathways, making them an interesting model to address fundamental questions in avian innate immune responses against emerging viral infections.
- To understand the innate immune responses in different avian hosts and bats that range from sensing of viruses to terminal IFN effectors mediated by a myriad of interferon-stimulated and virus-regulated genes.
- To decipher differential host responses to diverse avian pathogens, and understand the bases for genetic resistance/susceptibility of different avian and bat species, using large-scale, genome-wide and high throughput lentivirus-based screening platforms.
- We are also applying genome-wide transcriptomics and proteomics approaches to understanding molecular determinants of viral pathogenesis (infection) and the ways avian viruses (e.g. Newcastle disease virus, avian metapneumoviruses and influenza viruses) have adapted to avoid innate immune responses in avian hosts.
- We are cataloguing chicken interferon stimulated genes into groups using different methodologies. The information gained is being used in constructing cell lines that promote virus replication, and in vaccine production.
- We are investigating bat genomes as bats are reservoirs for several viral pathogens of significance to both human and animal health. It has been proposed that the host:pathogen interaction in bats is regulated by innate immune mechanisms, which are essentially controlled by interferon stimulated genes (ISGs). We are annotating the bats ISGs in the bat genomes, looking for expression dynamics of these genes, and to understand roles of bat ISGs in the replication of bat viruses in collaboration with the Animal and Plant Health Agency.
- We are apply state-of-the-art technologies in assessing most profound innate immune responses in wild birds and bats, and their possible significance in disease kinetics.This is a multi-institutional programme under the Newton Fund theme on “Institutional Links”, led by Infection and Innate Immunity group at The Pirbright Institute.
In response to viral infection, animals mount a prompt and effective resistance known as innate immunity. These innate responses act as first line of defense and cease the spread of virus infection within minutes to hours. We are applying next generation methodologies to understand the nature and dynamics of these innate responses against wide-range of viruses that are not only causing economical losses to the livestock industry but also can switch from animal to human.