Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants.
Pathogenesis of herpes simplex virus type 2 virion host shutoff (vhs) mutants.
复制标题
单纯疱疹病毒 2 型病毒粒子宿主关闭 (vhs) 突变体的发病机制。
DOI：
10.1128/jvi.76.5.2054-2061.2002
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发表时间：
2002
影响因子：
5.4
通讯作者：
Leib,DavidA
中科院分区：
文献类型：
--
作者：
Smith,TracyJ;Morrison,LyndaA;Leib,DavidA
During lytic infection, the virion host shutoff (vhs) protein mediates the rapid degradation of mRNA and the shutoff of host protein synthesis. In vivo, herpes simplex virus type 1 (HSV-1) mutants lackingvhsactivity are profoundly attenuated. Homologs ofvhsexist in all of the neurotropic herpesviruses, and the goal of this study was to determine the virulence of HSV-2 mutants lacking vhs. Two HSV-2 recombinants were used in this study: 333-vhsB, which has alacZcassette inserted into the N terminus ofvhs, and 333d41, which has a 939-bp deletion invhs. As expected, both 333-vhsB and 333d41 failed to induce the cellular RNA degradation characteristic of HSV. Corneal, vaginal, and intracerebral routes of infection were used to study pathogenesis. Both viruses grew to significantly lower titers in the corneas, trigeminal ganglia, vaginas, dorsal root ganglia, spinal cords, and brains of mice than wild-type and rescue viruses, with a correspondingly reduced induction of disease. Both viruses, however, reactivated efficiently from explanted trigeminal ganglia, showing thatvhsis dispensable for reactivation. The lethality of 333d41 following peripheral infection of mice, however, was significantly higher than that of 333-vhsB, suggesting that some of the attenuation of 333-vhsB may be due to the presence of alacZcassette in thevhslocus. Taken together, these data show thatvhsrepresents an important determinant of HSV-2 pathogenesis and have implications for the design of HSV-2 recombinants and vaccines.
