%0 Journal Article %A Gamlen, Toby %A Richards, Kathryn H. %A Mankouri, Jamel %A Hudson, Laura %A McCauley, John %A Harris, Mark %A Macdonald, Andrew %T Expression of the NS3 protease of cytopathogenic bovine viral diarrhea virus results in the induction of apoptosis but does not block activation of the beta interferon promoter %D 2010 %J Journal of General Virology, %V 91 %N 1 %P 133-144 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.016170-0 %I Microbiology Society, %X Bovine viral diarrhea virus (BVDV; genus Pestivirus) can exist as two biotypes, cytopathogenic (CP) and non-cytopathogenic (NCP). The CP form differs from NCP by the continual expression of free non-structural protein 3 (NS3). CP BVDV infection of cultured cells induces apoptosis, whereas NCP BVDV infection has been reported to block the induction of beta interferon (IFN-β). To investigate the viral mechanisms underlying these effects, NS3 or NS2–3 proteins of NCP and CP BVDV biotypes, together with the cognate NS3 co-factor NS4A, were expressed in cells, and their effect on apoptosis and induction of IFN-β was investigated. Expression of NS3/4A resulted in increased activity of caspase-9 and caspase-3, indicating induction of the intrinsic apoptosis pathway. Mutational analysis revealed that a protease-inactive NS3/4A was unable to induce apoptosis, suggesting that NS3 protease activity is required for initiation of apoptosis during CP BVDV infection. The ability of NS2–3 to modulate activation of the IFN-β promoter was also investigated. These studies confirmed that, unlike the related hepatitis C virus and GB virus-B, BVDV proteases are unable to inhibit TLR3- and RIG-I-dependent activation of the IFN-β promoter. These data suggest that BVDV NS3/4A is responsible for regulating the levels of cellular apoptosis and provide new insights regarding the viral elements associated with CP biotype pathogenesis. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.016170-0