Research focuses on viral pathogenesis and protection against large DNA viruses affecting domestic animal species. Orf virus (ORFV) is a poxvirus of the genus Parapoxvirus (PPV) that infects oral mucocutaneous tissues in sheep and goats worldwide. The virus causes operational infections in people in contact with diseased animals. ORFV preparations are used in Veterinary Medicine as a non-specific therapeutic immunomodulator in various animal species. While these preparations likely target trained immunity, the innate stimuli, viral proteins, and epigenetic reprogramming events that shape the induction are unknown. This feature together with other known poxviral attributes makes ORFV an attractive candidate for a vaccine viral vector. We have previously sequenced the full ORFV genome, and identified approximately 15 novel genes unique to PPV, with potential roles in the manipulation of host immune responses. Using recombinant virus mutants, molecular biology tools, and a sheep model of infection, we have characterized- and provided mechanistic insight for five inhibitors of the critical pro-inflammatory pathway NF-κB, and a modulator of the LPA-p38 kinase signaling pathway. Sheep infection phenotypes ranged from strong virus attenuation to no effect in virulence. Continuing work on the characterization of ORFV immunomodulatory proteins will allow fine-tuning of ORFV immunomodulatory properties that will result in more efficient and safer therapeutics and vaccine vectors.

African swine fever (ASF) is an acute, lethal disease of swine caused by ASF virus (ASFV). Devastating ASFV outbreaks and continuing epidemic in the Caucasus region, Russia and South East Asia highlight significance of the ASF disease threat for the swine industry worldwide. Despite the continual ASF threat and the fact the disease was first described in 1921, no ASF vaccine is available. Vaccination against ASF is possible since protection against homologous infection has been demonstrated; however, vaccine development has been hindered by large gaps in knowledge concerning ASFV infection and immunity, the extent of ASFV strain variation and the ASFV protective antigens responsible for inducing protective immune responses in the pig. In searching for ASFV protective antigens in collaboration with colleagues from the UIUC, UConn and institutes abroad, we have found that CD2v, the viral hemagglutinin, correlates strictly with current ASFV serogrouping, and mediates monocyte infection inhibition in a serogroup specific manner. Further, we found that ASFV CD2v and C-type lectin proteins are important for protection against homologous ASFV infection. Using IFN-ϒ ELISpot assay and PBMCs from ASF immune animals, six T-cell epitopes were identified in these proteins. We have recently shown that ASFV CD2v protein induces β-Interferon expression and apoptosis in swine peripheral blood mononuclear cells, suggesting CD2v may be a significant virulent factor in the massive lymphocyte apoptosis observed in lymphoid tissue during ASFV infection in pigs.