Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

The porcine reproductive and
respiratory syndrome virus (PRRSV) and the porcine epidemic diarrhea virus
(PEDV) are responsible for severe agricultural economic losses and are
considered to be the primary emerging livestock pathogens in Canada and worldwide.
Both viruses are single-stranded, positive-sense RNA, enveloped porcine
nidoviruses and share common characteristics including similar particle
structure, conserved genomic organization and replication strategy. The
traditional approach to develop vaccines has not resulted in reliable and
effective vaccines, and these viruses remain a major threat to the swine
industry worldwide.
We believe that insufficient
understanding of nidovirus-host interactions hinders the development of
effective vaccines against nidoviruses. Therefore , we propose to investigate the molecular mechanisms of animal
nidovirus-host interactions in order to identify novel antiviral targets and
develop effective prevention strategies.
The
long-term goal of this program is to gain a better understanding of the molecular
mechanisms of interactions between animal nidoviruses and their hosts in order
to develop new strategies for effective control of viral infections. The short-term
goal for the next five years is to elucidate PRRSV and PEDV interactions with
host cells by focusing on the characterization and comparison of early events
in nidovirus infection. To address this objective, we will: 1) investigate the
cellular and molecular mechanisms underlying porcine nidovirus entry into host
cells, and 2) analyze proteomic profiles of host cell responses to viral
infection, characterize the composition of nidoviruses, and identify the host
proteins associated with the viral particle. The accomplishment of these
specific objectives will lead to an understanding of the nature of the
virus-host interaction during the earliest stage of nidovirus infection. We
will identify cellular factors interacting with the viral genome and proteins,
as well as host proteins that are incorporated into viral particles and
involved in modulation of viral infection. We will map the highly conserved and
potent antigenic epitopes of viral proteins, which are transiently exposed
during the process of virus entry and represent important targets for vaccine
design. These results will provide tools and directions for the continuation of
our research program in the investigation of intracellular trafficking of the viral
genome and proteins within the host cell, the mechanisms of viral assembly and
release, and the cellular pathways exploited and rearranged by nidoviruses to
facilitate infection and evade host surveillance. More importantly, our
findings will provide new specific targets for antiviral vaccine development. Our
findings will also be relevant to many other enveloped animal viruses .