[Skip to content]

The Pirbright Institute
.

Innate Immunity and Host Genetic Diversity

Innate Immunity and Host Genetic Diversity

Interaction of virus with the host is fundamental to initiate an infection and to complete a successful 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 player, interferons (IFN). The induction of IFNs is generic but the terminal actions can be host and pathogen specific, and is contributed by the IFN-stimulated or virus-regulated proteins. In this context, chicken is unique since even in the updated version of chicken genome, it appears that chicken lack crucial elements in JAK/STAT pathway (IFN signalling). Moreover, current release of the 48 consistently annotated birds genomes, spanning 32 of the 35 recently proposed avian orders, has confirmed that “bird genomes are smaller than other vertebrate genomes. They have less repetitive DNA and have lost 7% of the genes - 58 million bases in total – found in the lizard cousin, the anole”.

In the “Innate Immunity and Host Genetic Diversity Group” we aim to understand the innate immune responses in different avian hosts that range from sensing of viruses to terminal IFN effectors mediated by myriad interferon stimulated genes (Fig. 1). We have adapted large-scale, genome-wide and high throughput lentivirus-based screening platforms to investigate, both generically and specifically, the interaction of viruses with host immune responses (Fig. 2, 3), deciphering differential host responses to diverse avian pathogen, and the bases for genetic resistance/susceptibility of different avian species. In addition to avian species, we are investigating the roles of bats interferon stimulated genes against different bat viruses through our recently funded Royal Society grant.

We are also investigating the strategies that viruses use to escape from host defences. Using reverse-genetics systems for Newcastle disease virus and avian metapneumoviruses, we are applying genome-wide transcriptomics and proteomics approaches to understanding the molecular determinants of viral pathogenesis and the ways viruses have adapted to circumvent these responses.

Projects:

Research in this group is supported by the following national and international funding agencies:


BBSRC-FAPESP Collaborative Research Grant on Avian Innate Immunity:


BBSRC logo
       

FAPESP


Royal Society Research Grant on Bats Immunity with Special Reference to Bats Interferon Stimulated Genes:

 

Royal Society

BBSRC: Genetic Diversity of Wild Birds and Virus Evolution:


Brazil Award

 

British Council: Construction of Genotype-Matched Newcastle disease vaccine.

British Council

Swedish Research Council: Role of Wild Ruminants on Virus Emergence

SRC

Edited and Authored Books:

CABI
Mononegaviruses of Veterinary Importance Vol I: Pathobiology and Molecular Diagnosis
         

More information at: Home Page of the Book

PPRV-Edited 2015
Peste des Petits Ruminants Virus

More information at: Home Page of the Book

PPRV_Authored 2014
Molecular Biology and Pathogenesis of Peste des Petits Ruminants Virus

More information at: Home Page of the Book




Research Leader:


Group Member:

Manoja Rasamanikkam


External Links:

           

(Participate in the First GARAD Meeting in London from June 29 to July 01, 2015 More info)


[ Zoom ]
ISG
Fig. 1: Mechanism of IFN induction by viruses and transcriptional regulation of ISGs in mammals. Few most characterised ISGs are highlighted at extreme right. ©MM
[ Zoom ]
lentivirus
Fig. 2: Lentivirus based screening strategy
[ Zoom ]
ZAPs
Fig. 3: Expression of zinc finger CCCH type, antiviral 1 (Zc3hav1), an ISG, in DF-1 cells stimulated with Newcastle diseases virus (a), at high magnification (b). Rescue of a lentivirus showing bicistronic expression of RFP and Zc3hav1 in 293-T cells (c).

External Links


Contact us

Please email us at enquiries@pirbright.ac.uk.