Raggo Camilo, Habermehl Monique, Babiuk Lorne A, Griebel Philip
Department of Veterinary Microbiology1 and Veterinary Infectious Disease Organization2, 120 Veterinary Road, University of Saskatchewan, Canada S7N 5E3.
J Gen Virol. 2000 Nov;81(Pt 11):2665-2673. doi: 10.1099/0022-1317-81-11-2665.
To study the biological relevance of using bovine herpesvirus-1 (BHV-1) as a vector for expressing cytokines, a BHV-1 virus that expressed bovine interferon-gamma (IFN-gamma) was constructed. This recombinant virus (BHV-1/IFNgamma) was then used to infect the natural host in a respiratory disease model. In vitro characterization of the recombinant interferon-gamma confirmed that the cytokine expressed in BHV-1-infected cells was biologically active. The in vivo effects of the recombinant IFN-gamma were then analysed during a primary infection and after reactivation of a latent infection. During the primary infection, similar body temperature, clinical responses and virus shedding were observed for calves infected with either recombinant BHV-1/IFNgamma or parental gC(-)/LacZ(+) virus. An analysis of cellular and humoral responses did not reveal any significant immunomodulation by BHV-1/IFNgamma during the primary infection. The stability and activity of recombinant IFN-gamma was also analysed following the establishment of a latent infection. The presence of recombinant IFN-gamma did not significantly alter virus shedding following reactivation. The isolation of reactivated BHV-1/IFNgamma virus confirmed that a functional IFN-gamma gene was retained during latency. Thus, herpesviruses may provide virus vectors that retain functional genes during latency and recrudescence.
为研究使用牛疱疹病毒1型（BHV-1）作为表达细胞因子载体的生物学相关性，构建了一种表达牛γ干扰素（IFN-γ）的BHV-1病毒。然后将这种重组病毒（BHV-1/IFNγ）用于呼吸道疾病模型中感染天然宿主。对重组γ干扰素的体外特性分析证实，在BHV-1感染细胞中表达的细胞因子具有生物活性。随后在初次感染期间以及潜伏感染重新激活后分析了重组IFN-γ的体内作用。在初次感染期间，感染重组BHV-1/IFNγ或亲本gC(-)/LacZ(+)病毒的犊牛观察到相似的体温、临床反应和病毒排出情况。对细胞和体液反应的分析未发现BHV-1/IFNγ在初次感染期间有任何显著的免疫调节作用。在潜伏感染建立后还分析了重组IFN-γ的稳定性和活性。重组IFN-γ的存在在重新激活后并未显著改变病毒排出情况。重新激活的BHV-1/IFNγ病毒的分离证实，在潜伏期间功能性IFN-γ基因得以保留。因此，疱疹病毒可能提供在潜伏和复发期间保留功能基因的病毒载体。
