Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model
Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model
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DOI：
10.1006/viro.2000.0628
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发表时间：
2000-12-05
期刊：
影响因子：
3.7
通讯作者：
Knipe, DM
中科院分区：
文献类型：
--
作者：
Jones, CA;Taylor, TJ;Knipe, DM
我们使用小鼠鼻腔感染单纯疱疹病毒2 （HSV-2）模型，在体内检测HSV-2野生型（wt）、tk阴性和复制缺陷株的生物学特性。鼻中隔组织是鼻内接种后wt病毒复制的主要部位。HSV-2毒株186 syn(+)-1 wt病毒在每鼻孔10(4)PFU及以上剂量下可引起致死性脑炎，而在较低剂量下，三叉神经节中没有潜伏期相关转录物阳性的神经元，表明缺乏潜伏性感染。186 Delta Kpn tk阴性突变病毒在鼻中隔组织中复制，但仅在一个时间点在三叉神经节中显示低水平复制。三叉神经节原位杂交显示，lat阳性神经元数量与接种剂量成正比，接种剂量为10(3)~ 10(6)PFU / n。复制缺陷突变病毒5B/acZ在鼻中隔组织中没有复制，在接种部位和三叉神经节中没有病毒DNA的持久性。然而，在远端部位接种5B/acZ或双突变型d/5-29可减少186 Delta Kpn在鼻内侵染后的急性复制和潜伏感染。该感染模型提供了一个生物学系统来测试HSV-2毒株的特性，并表明复制缺陷突变毒株不会在接种部位或感觉神经节中持续存在，但可以诱导免疫保护，减少攻击病毒的潜伏病毒载量。(C) 2000年学术出版社。
We used a mouse nasal model of herpes simplex virus 2 (HSV-2) infection to examine the biological properties of HSV-2 wild-type (wt), TK-negative, and replication-defective strains in vivo. Nasal septa tissue is the major site of wt viral replication post intranasal (i.n.) inoculation. The HSV-2 strain 186 syn(+)-1 wt virus caused lethal encephalitis at doses of 10(4) PFU and above per nostril, and at lower doses no neurons in the trigeminal ganglia were positive for the latency-associated transcript, indicating a lack of latent infection. The 186 Delta Kpn TK-negative mutant virus replicated in nasal septa tissue but showed low-level replication in trigeminal ganglia at only one timepoint. In situ hybridization of trigeminal ganglia showed that the number of LAT-positive neurons was proportional to the inoculum dose from 10(3) to 10(6) PFU per nare. The replication-defective mutant virus 5B/acZ showed no replication in nasal septa tissue and no persistence of viral DNA at the inoculation site or the trigeminal ganglia. Nevertheless, inoculation of 5B/acZ or the double-mutant d/5-29 at distal sites reduced acute replication and latent infection of 186 Delta Kpn following intranasal challenge. This infection model provides a biological system to test the properties of HSV-2 strains and shows that replication-defective mutant strains do not persist at sites of inoculation or in sensory ganglia but can induce immune protection that reduces the latent viral load of a challenge virus. (C) 2000 Academic Press.