Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission
Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission
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DOI：
10.1128/jvi.75.23.11821-11826.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Cunningham, AL
中科院分区：
文献类型：
--
作者：
Mikloska, Z;Cunningham, AL
通过体外双室模型研究了α干扰素（ifn - α）和α干扰素（ifn - γ）抑制I型单纯疱疹病毒（HSV-1）从神经元轴突向表皮细胞（ECs）传播并在表皮细胞中传播的能力，并与表皮外植体直接感染HSV-1进行了比较。在hsv -1感染的DRG神经元轴突传播后，在外室的ECs中以浓度依赖的方式添加重组ifn - γ和ifn - α，可显著减少ECs中病毒细胞病变斑块的数量和大小。在感染HSV-1的同时加入ifn对DRG的抑制作用最大。ifn - α组平均斑块数量减少52%，ifn - γ组减少36%，ifn - α和ifn - γ联合使用时减少62%，平均斑块大小分别减少64%、43%和72%。直接感染EC外植体后，两种干扰素的抑制作用相似但较弱，在同时添加干扰素或感染HSV-1前6 h时抑制作用最大。这些结果表明，ifn - α和ifn - γ都可以通过直接抗病毒作用干扰HSV-1轴突传播后的感染和随后的HSV-1在ec中的传播。因此，ifn - α和- γ都可能有助于控制HSV-1的传播和脱落，在复发性疱疹病变中以类似的方式。
The ability of alpha interferon (IFN-alpha) and IFN-gamma to inhibit transmission of herpes simplex virus type I (HSV-1) from neuronal axon to epidermal cells (ECs), and subsequent spread in these cells was investigated in an in vitro dual-chamber model consisting of human fetal dorsal root ganglia (DRG) innervating autologous skin explants and compared with direct HSV-1 infection of epidermal explants. After axonal transmission from HSV-1-infected DRG neurons, both the number and size of viral cytopathic plaques in ECs was significantly reduced by addition of recombinant IFN-gamma and IFN-alpha to ECs in the outer chamber in a concentration-dependent fashion. Inhibition was maximal when IFNs were added at the same time as the DRG were infected with HSV-1. The mean numbers of plaques were reduced by 52% by IFN-alpha, 36% by IFN-gamma, and by 62% when IFN-alpha and IFN-gamma were combined, and the mean plaque size was reduced by 64, 43, and 72%, respectively. Similar but less-inhibitory effects of both IFNs were observed after direct infection of EC explants, being maximal when IFNs were added simultaneously or 6 h before HSV-1 infection. These results show that both IFN-alpha and IFN-gamma can interfere with HSV-1 infection after axonal transmission and subsequent spread of HSV-1 in ECs by a direct antiviral effect. Therefore, both IFN-alpha and -gamma could contribute to the control of HSV-1 spread and shedding in a similar fashion in recurrent herpetic lesions.