RNA recombination in pestiviruses: cellular RNA sequences in viral genomes highlight the role of host factors for viral persistence and lethal disease.

Persistence of the positive strand RNA virus bovine viral diarrhea virus (BVDV) in its host may last for years. However, it frequently ends in lethal disease triggered by emerging virus mutants created by RNA recombination. Those mutant genomes often encompass cellular mRNA fragments. Persistence of BVDV depends on a mechanism limiting viral RNA replication efficiency. This restriction is based on the dependency of a viral protease on a cellular cofactor available only in limiting amounts. Virus mutants leading to progression from persistence to lethal disease elude this regulatory mechanism by various genomic changes achieved by RNA recombination. Cell culture based studies on the underlying mechanisms demonstrated that RNA recombination occurs even in the absence of an active viral RNA-dependent RNA polymerase. This implicates that mechanisms besides the commonly accepted replicative template switching model are involved in viral RNA recombination.