Coleman Heather M, de Lima Brigitte, Morton Victoria, Stevenson Philip G
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
J Virol. 2003 Feb;77(4):2410-7. doi: 10.1128/jvi.77.4.2410-2417.2003.
The lytic cycle functions of gammaherpesviruses have received relatively little attention to date, at least in part due to the lack of a convenient experimental model. The murine gammaherpesvirus 68 (MHV-68) now provides such a model and allows the roles of individual lytic cycle gammaherpesvirus proteins to be evaluated in vivo. We have used MHV-68 to determine the contribution of a gammaherpesvirus thymidine kinase (TK) to viral lytic replication and latency establishment. MHV-68 mutants with a disrupted TK gene grew normally in vitro but showed a severe attenuation of replication in the lungs after intranasal inoculation, with lytic titers at least 1,000-fold lower than those of wild-type and revertant viruses. Nevertheless, the establishment of latency by the TK-deficient mutants, while delayed, was not prevented by their lytic replication deficit. The viral TK clearly plays a crucial role in the capacity of MHV-68 to replicate efficiently in its natural host but does not seem to be essential to establish a persistent infection. The potential of TK-deficient mutants as gammaherpesvirus vaccines is discussed.
迄今为止，γ疱疹病毒的裂解周期功能受到的关注相对较少，至少部分原因是缺乏方便的实验模型。小鼠γ疱疹病毒68（MHV - 68）现在提供了这样一个模型，并使得能够在体内评估单个γ疱疹病毒裂解周期蛋白的作用。我们利用MHV - 68来确定γ疱疹病毒胸苷激酶（TK）对病毒裂解复制和潜伏建立的贡献。TK基因被破坏的MHV - 68突变体在体外正常生长，但鼻内接种后在肺部的复制表现出严重减弱，其裂解滴度比野生型和回复病毒至少低1000倍。然而，TK缺陷突变体潜伏的建立虽然延迟，但并未因其裂解复制缺陷而受到阻碍。病毒TK显然在MHV - 68在其自然宿主中高效复制的能力中起着关键作用，但似乎对于建立持续感染并非必不可少。文中还讨论了TK缺陷突变体作为γ疱疹病毒疫苗的潜力。
