Uniocular anterior chamber inoculation of a tumor necrosis factor alpha-expressing recombinant of herpes simplex virus type 1 results in more rapid destruction and increased viral replication in the retina of the uninoculated eye.
Uniocular anterior chamber inoculation of a tumor necrosis factor alpha-expressing recombinant of herpes simplex virus type 1 results in more rapid destruction and increased viral replication in the retina of the uninoculated eye.
复制标题
单眼前房接种表达肿瘤坏死因子 α 的 1 型单纯疱疹病毒重组体，可导致未接种眼视网膜更快的破坏和病毒复制的增加。
DOI：
10.1128/jvi.00082-08
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发表时间：
2008
影响因子：
5.4
通讯作者：
Atherton,SallyS
中科院分区：
文献类型：
--
作者：
Fields,MarkA;Zheng,Mei;Wall,Pam;Oberg,Scott;Atherton,SallyS
肿瘤坏死因子α (TNF-α)已被证明在1型单纯疱疹病毒（HSV-1）感染小鼠的眼睛和大脑中具有保护作用。为了确定TNF-α的过表达是否影响单眼前房接种后病毒感染的过程，构建了重组HSV-1组成性产生TNF-α (KOSTNF)。分别给BALB/c小鼠注射TNF-α重组体、含有pCI质粒的重组体、重组救援病毒或亲本病毒。采用流式细胞术和免疫组织化学技术鉴定病毒感染细胞，并确定未注射眼内浸润炎性细胞的数量和类型。用空斑法测定病毒滴度。各组间病毒滴度、病毒在注射眼或视交叉上核传播的途径和时间均无差异。而在未注射kostnf感染小鼠的眼睛中，TNF-α表达升高，病毒抗原阳性细胞和免疫炎症细胞增多。这些小鼠视网膜感染和破坏的显微镜证据较早，感染kostnf的小鼠在感染后第7天未注射的眼睛中的病毒滴度与感染KOSpCI-， kos6 β拯救-或kos6 β感染的小鼠相比显着增加。结果表明，TNF-α的过度表达不是减缓感染和减少病毒传播，而是由于增加炎症和病毒感染导致未接种眼睛的视网膜早期破坏而具有有害影响。
Tumor necrosis factor alpha (TNF-α) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-α affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-α constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-α recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-α expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6βrescue-, or KOS6β-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-α has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.