Inhibition or evasion of immunity are strategies that all viruses have evolved, and long-lasting, asymptomatic infection is a hallmark characteristic of an optimally attuned virus-host adaptation. Molluscum Contagiosum virus (MCV) is the only known poxvirus that appears to be specifically adapted to human infection. MCV infections are common, particularly in developing countries and it results in the formation of distinct, contagious, papular skin lesions. Notably, these lesions have little, or no inflammation associated with them (unlike skin lesions of historical variola and vaccinia infection). Such lesions persist for long periods without an apparent response from the host suggesting MCV possesses a potent array of immunosuppressive genes, yet more than 90% of its genome remains uncharacterised. Screening of the MCV genome identified MC008 as a potential inhibitor of innate immune signalling. Mass spectrometry analysis of co-purifying proteins identified that MC008 interacts with the STING-regulating protein TRIM32. MC008 targets TRIM32 in the cGAS-STING pathway in human cells and appears to inhibit TRIM32-driven polyubiquitination of STING, preventing this positive regulatory step in NFκB but not ISRE activation. Furthermore, we have identified NEMO as another target of MC008, suggesting a possible mechanism by which TRIM32-generated polyubiquitin chains are disrupted from inducing NEMO activation. By understanding the mechanism by which this potent inhibitor functions to inhibit this key sensing DNA pathway, we aim to use these findings to design new strategies for therapeutic intervention where these pathways are dysregulated in disease.

Molluscum Contagiosum Virus Protein MC008 is a Novel Inhibitor of Human NFκB

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.