Jacobson J G, Chen S H, Cook W J, Kramer M F, Coen D M
Program in Virology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Virology. 1998 Mar 1;242(1):161-9. doi: 10.1006/viro.1997.9012.
The UL24 gene of herpes simplex virus overlaps the viral thymidine kinase (tk) gene. Most previous studies of UL24 have examined UL24 mutants that have also contained tk and sometimes other mutations. To address the importance of UL24 for viral replication in cell culture and in infections of a mammalian host, we constructed a mutant virus containing a UL24 nonsense mutation that does not affect TK activity and a second mutant that contains clustered point mutations in UL24 and a mutation in tk that does not by itself affect the ability of the virus to replicate acutely in mouse ganglia or to reactivate from latent infection following corneal inoculation of mice. Both mutant viruses replicated in cells in culture and in the mouse eye, albeit less efficiently than wild type or control viruses. Both mutants were much more severely impaired for acute replication in trigeminal ganglia and for reactivation from latency following explant of these ganglia. Viral DNA and latency-associated transcripts were present, albeit at lower levels in ganglia infected with the nonsense mutant. These results indicate that UL24 is especially important for productive infection of mouse sensory ganglia and may have implications for the behaviors of certain tk mutants in pathogenesis.
单纯疱疹病毒的UL24基因与病毒胸苷激酶（tk）基因重叠。以往大多数关于UL24的研究都检测了同时含有tk以及有时还含有其他突变的UL24突变体。为了探讨UL24在细胞培养和哺乳动物宿主感染中对病毒复制的重要性，我们构建了一种突变病毒，其含有不影响TK活性的UL24无义突变，以及另一种突变病毒，其在UL24中含有成簇的点突变且在tk中有一个突变，该tk突变本身并不影响病毒在小鼠神经节中急性复制或在小鼠角膜接种后从潜伏感染中重新激活的能力。两种突变病毒都能在培养细胞和小鼠眼中复制，尽管效率低于野生型或对照病毒。两种突变体在三叉神经节中的急性复制以及这些神经节外植后从潜伏状态重新激活方面都受到更严重的损害。病毒DNA和潜伏相关转录本存在，尽管在感染无义突变体的神经节中水平较低。这些结果表明，UL24对小鼠感觉神经节的有效感染尤为重要，并且可能对某些tk突变体在发病机制中的行为有影响。
