The in vivo effects of recombinant bovine herpesvirus-1 expressing bovine interferon-gamma

To study the biological relevance of using bovine herpesvirus-l (BHV-1) as a vector for expressing cytokines, a BHV-1 virus that expressed bovine inte rferon-gamma (IFN-gamma) was constructed. This recombinant virus (BHV-1/IFN gamma) was then used to infect the natural host in a respiratory disease m odel. In vitro characterization of the recombinant interferon-gamma confirm ed that the cytokine expressed in BHV-1-infected cells was biologically act ive. The in vivo effects of the recombinant IFN-gamma were then analysed du ring a primary infection and after reactivation of a latent infection. Duri ng the primary infection, similar body temperature, clinical responses and virus shedding were observed for calves infected with either recombinant BH V-1/IFN gamma, or parental gC(-)/LacZ(+) virus. An analysis of cellular and humoral responses did not reveal any significant immunomodulation by BHV-1 /IFN gamma during the primary infection. The stability and activity of reco mbinant IFN-gamma was also analysed following the establishment of a latent infection. The presence of recombinant IFN-gamma did not significantly alt er virus shedding following reactivation, The isolation of reactivated BHV- 1/IFN gamma virus confirmed that a functional IFN-gamma gene was retained d uring latency. Thus, herpesviruses may provide virus vectors that retain fu nctional genes during latency and recrudescence.