The interaction of pestiviruses with their host cells to manipulate and evade the innate and, therefore, also the adaptive immune system
Bovine viral diarrhea virus (BVDV; genus Pestivirus in the family Flaviviridae) evades the host's innate immune system, e.g., by efficiently blocking the interferon synthesis. This might explain the success of this virus to cause persisting infection and immunotolerance and, thus, to persist in the host population. BVDV is a unique model to study many aspects of the virus in its natural setting. Due to the complete immune-tolerance specific to the infecting virus strain, this model allows to thoroughly investigate the viral immune evasion mechanisms in the absence of adaptive immune responses. Additionally, we study a natural pathogen of cattle, and we are convinced that we can largely benefit from studying diseases caused by pathogens that have co-evolved with their hosts.
One core area is the soluble viral glycoprotein Erns that exhibits an unusual RNase activity distinguished from the endogenous RNases present in bovine serum. Excitingly, these data may offer a new hypothesis for the role of Erns, i.e., it may prevent the host’s innate immune system from detecting the virus as “nonself” and inducing a strong interferon (IFN) response. Thus, pestiviruses might induce a form of “innate immunotolerance”, and this might also address more fundamental question that goes beyond that of the mechanism of a cattle disease, namely on the mechanisms that enable the host to differentiate between “self RNA” and “viral nonself RNA”. Accordingly, we have common projects to study persistent infections with small ruminant lentiviruses and to investigate the interaction of canine distemper virus (CDV, a paramyxovirus related the measles virus) with its host cells to evade innate immunity.
As Swiss reference laboratory for pestiviruses, we participate in the development of diagnostics tests and in applied research projects to further understand transmission and pathogenesis of pestiviral infections in collaboration with Prof. R. Zanoni (head diagnostics IVI-Bern) and his team.
Funding: SNF; FSVO; IVI