The involvement of oxidative stress in bovine herpesvirus type 4-mediated apoptosis.

Bovine herpesvirus type 4 (BHV-4) belongs to the gamma-2-herpesviruses of the Gammaherpesvirinae subfamily. BHV-4 has a worldwide distribution and has been isolated in a variety of clinical diseases as well as from healthy cattle. In this report we demonstrate that BHV-4 induces apoptosis in MDBK cells. In the early phases of apoptosis, cells show an increase in the intracellular level of reactive oxygen species, which is indicative of oxidative stress. This precedes DNA fragmentation, a hallmark typical of apoptosis. Cells were protected from apoptosis only by certain antioxidants (butylated hydroxyanisole and ebselen), whereas N-acetylcysteine turned out to be ineffective. Antioxidants that protected cells from apoptosis prevented oxidative stress but failed to block virus growth. These observations suggest that oxidative stress may be a crucial event in the sequence leading to apoptotic cell death but apoptosis is not required for the multiplication of BHV-4.