单纯疱疹病毒1型（HSV-1）糖蛋白K（gK）对于病毒在角膜的传播和神经侵袭至关重要。

The herpes simplex virus type 1 (HSV-1) glycoprotein K(gK) is essential for viral corneal spread and neuroinvasiveness.

作者信息

David Andrew T, Baghian A, Foster T P, Chouljenko V N, Kousoulas K G

机构信息

Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA.

出版信息

Curr Eye Res. 2008 May;33(5):455-67. doi: 10.1080/02713680802130362.

DOI:10.1080/02713680802130362

PMID:18568883

Abstract

PURPOSE

To determine the role of herpes simplex virus-1 (HSV-1) glycoprotein K(gK) in corneal infection, neuroinvasion, and virus latency in trigeminal ganglia of mice.

METHODS

The recombinant virus HSV-1 (McKrae) Delta gK (MKDelta gK) carrying a deletion of the gK gene was constructed by insertional/deletion mutagenesis and replaced by a gene cassette constitutively expressing the enhanced green fluorescence protein. The gK deletion of the MKDelta gK virus was rescued to produce the wild-type-like virus MKgK. Balb/c mice were infected ocularly with either virus, and the infection pattern in the eye, clinical disease progression, and establishment of viral latency was monitored.

RESULTS

Mice infected with the MKDelta gK strain produced in a gK complementing cell line did not exhibit clinical signs when compared with mice infected with the MKgK virus. Direct visualization of infected eyes revealed that the MKDelta gK virus was unable to spread in mouse corneas, while the MKgK rescued virus spread efficiently. Nineteen of 20 scarified and 5/12 unscarified mice infected with the MKgK virus produced infectious virus after coculture with permissive cells, while 0/20 scarified and 0/12 unscarified mice infected with the MKDelta gK virus produced infectious virus. HSV DNA was detected in trigeminal ganglia by PCR in 19/20 scarified and 9/12 unscarified mice inoculated with MKgK, while HSV DNA was detected in the trigeminal ganglia of 3/20 scarified and 0/12 unscarified mice inoculated with MKDelta gK.

CONCLUSIONS

The results show that HSV-1 gK is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglia neuroinvasion in MKDelta gK inoculated mice.

摘要

目的

确定单纯疱疹病毒1型（HSV-1）糖蛋白K（gK）在小鼠角膜感染、神经侵袭及三叉神经节病毒潜伏中的作用。

方法

通过插入/缺失诱变构建携带gK基因缺失的重组病毒HSV-1（McKrae）ΔgK（MKΔgK），并用组成型表达增强型绿色荧光蛋白的基因盒进行替换。对MKΔgK病毒的gK缺失进行挽救以产生野生型样病毒MKgK。用这两种病毒分别对Balb/c小鼠进行眼部感染，并监测眼睛中的感染模式、临床疾病进展及病毒潜伏的建立情况。

结果

与感染MKgK病毒的小鼠相比，感染在gK互补细胞系中产生的MKΔgK毒株的小鼠未表现出临床症状。对感染的眼睛进行直接观察发现，MKΔgK病毒无法在小鼠角膜中传播，而挽救后的MKgK病毒能有效传播。20只接种MKgK病毒的划痕小鼠中有19只、12只未划痕小鼠中有5只在与允许性细胞共培养后产生了感染性病毒，而接种MKΔgK病毒的20只划痕小鼠和12只未划痕小鼠中均无产生感染性病毒的情况。通过PCR在20只接种MKgK的划痕小鼠中有19只、12只未划痕小鼠中有9只的三叉神经节中检测到HSV DNA，而在接种MKΔgK的20只划痕小鼠中有3只、12只未划痕小鼠中均未在三叉神经节中检测到HSV DNA。