Chen Shih-Heng, Lin Yu-Wen, Griffiths Anthony, Huang Wen-Yen, Chen Shun-Hua
Institute of Basic Medical Sciences and Department of Microbiology and Immunology, Medical College, National Cheng Kung University, Tainan 70101, Taiwan, Republic of China.
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227, USA.
J Gen Virol. 2006 Dec;87(Pt 12):3495-3502. doi: 10.1099/vir.0.82223-0.
Laboratory strains of herpes simplex virus lacking thymidine kinase (TK) cannot replicate acutely to detectable levels in mouse trigeminal ganglia and do not reactivate from latency. However, many pathogenic clinical isolates that are resistant to the antiviral drug acyclovir are heterogeneous populations of TK-negative (TK(-)) and TK-positive (TK(+)) viruses. To recapitulate this in vivo, mice were infected with mixtures of wild-type virus and a recombinant TK(-) mutant in various ratios. Following co-infection, the replication, number of latent viral genomes and reactivation efficiency of TK(+) virus in trigeminal ganglia were reduced in a manner related to the amount of TK(-) virus in the inoculum. TK(+) virus did not always complement the acute replication or increase the number of latent viral genomes of TK(-) mutant in mouse ganglia. Even so, TK(+) virus could still confer the pathogenic phenotype to a TK(-) mutant, somehow providing sufficient TK activity in trans to permit a TK(-) mutant to reactivate from latently infected ganglia.
缺乏胸苷激酶（TK）的单纯疱疹病毒实验室毒株无法在小鼠三叉神经节中急性复制到可检测水平，也不会从潜伏状态重新激活。然而，许多对抗病毒药物阿昔洛韦耐药的致病性临床分离株是TK阴性（TK(-)）和TK阳性（TK(+)）病毒的异质群体。为了在体内重现这种情况，用不同比例的野生型病毒和重组TK(-)突变体混合物感染小鼠。共感染后，三叉神经节中TK(+)病毒的复制、潜伏病毒基因组数量和重新激活效率以与接种物中TK(-)病毒量相关的方式降低。TK(+)病毒并不总是能补充TK(-)突变体在小鼠神经节中的急性复制或增加潜伏病毒基因组数量。即便如此，TK(+)病毒仍能赋予TK(-)突变体致病表型，以某种方式在反式中提供足够的TK活性，使TK(-)突变体从潜伏感染的神经节中重新激活。
