RESEARCH SUMMARY

The Birnaviridae family groups icosahedral naked viruses with bipartite dsRNA genomes. Members of this family infect a wide variety of animal species including insects, aquatic fauna and birds. Some of these viruses cause diseases of great socio-economic significance.

Our main virus model is the infectious bursal disease virus (IBDV), the etiological agent of an acute immunosuppressive disease affecting domestic chickens. Our group is mainly interested in birnavirus structure and morphogenesis; and in the molecular basis for IBDV virulence.

We have continued our molecular analysis of the IBDV assembly centered on the role of the multi-functional VP3 polypeptide and the precursor of the capsid polypeptide (VP2). The characterization of the particle structure led us to demonstrate that the largest fraction of infectious IBDV particles contain four genome segments, thus providing the first evidence about the existence of icosahedral viruses with polyploid genomes. These studies led to the observation that the inner capsid space of the IBDV particles is occupied by a ribonucleoprotein (RNP) complex formed by the dsRNA genome associated to the VP3 polypeptide and the RNA dependent RNA polymerase (RdRp).

The presence of birnavirus RNPs represents a sharp divergence with respect to prototypical icosahedral dsRNA viruses whose genomes remain enclosed within an inner capsid (T=2) known as transcriptional core. The unique birnavirus structural and functional configuration pose major questions about their replicative strategy, i.e. the mechanisms for RNA transcription and replication mechanisms, and those used to counteract cellular dsRNA sensors and control host-cell innate immune responses. We are currently focusing a great deal of effort to functional characterization of the VP3 polypeptide. This multifunctional and highly conserved protein that plays different roles during virus replication and morphogenesis is a key element responsible for the control of the host’s innate antiviral responses.

As part of our work on virus-host interactions, we have identified the α4β1 integrin as the major IBDV binding receptor. IBDV cell binding entails the recognition of a strictly conserved sequence motif located in the projection domain of the capsid polypeptide by the α4β1 heterodimer. Additionally, we have shown that under certain conditions IBDV is capable of establishing persistent infections in chicken lymphocytes. These studies have opened new venues to characterize the mechanism of IBDV entry, and the molecular determinants for virus tropism, and for the development of new strategies to control IBDV infection.