The relationship between the viral RNA level and upregulation of innate immunity in spleen of cattle persistently infected with bovine viral diarrhea virus

Persistent infection in cattle with bovine viral diarrhea virus (BVDV), which is classified in the genus Pestivirus, family Flaviviridae, may result in growth retardation and immunosuppression. In vitro infection with noncytopathogenic (ncp) BVDV has been shown to suppress interferon (IFN) responses, whereas ncpBVDV induces transient strong IFN responses in vivo following acute infection of naïve cattle. In this study, the innate immune response of the spleen, a crucial organ for immune system homeostasis, from PI cattle was analyzed. The transcription of five IFN- and apoptosis-related mRNAs (Mx1, iNOS, OAS-1, PKR, and TNF-α), which was upregulated in response to BVDV replication in our previous in vitro studies, and the level of viral RNA were quantified using real-time RT-PCR. Upregulation of Mx1, OAS-1, PKR, and TNF-α mRNA expression was detected in the spleens of PI cattle regardless of their age, and induction of apoptosis was also upregulated in the spleens of PI cattle compared with those of nonPI cattle. Although it cannot be excluded that the innate immune responses may be activated in response to any secondary infections in immunosuppressed cattle, the absence of any pathogenic microorganisms in the PI cattle and the statistically significant correlation between innate immune responses and the viral RNA level indicates that there may be a positive relationship between the increased level of viral RNA replication and upregulation of innate immunity in vivo.