Bioluminescence imaging reveals systemic dissemination of herpes simplex virus type 1 in the absence of interferon receptors
Bioluminescence imaging reveals systemic dissemination of herpes simplex virus type 1 in the absence of interferon receptors
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DOI：
10.1128/jvi.77.20.11082-11093.2003
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发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Leib, DA
中科院分区：
文献类型：
--
作者：
Luker, GD;Prior, JL;Leib, DA
单纯疱疹病毒1型（HSV-1）可在新生儿和患有AIDS或其他免疫功能低下疾病的患者中产生播散性全身感染，尽管进行抗病毒治疗，仍导致显著的发病率和死亡率。通常限制HSV-1局部上皮和神经元感染的宿主免疫组分仍然不完全确定。我们使用体内生物发光成像来确定I型和II型干扰素（IFN）对I型、II型或I型和II型IFN受体遗传缺陷小鼠中HSV-1感染的复制和嗜性的影响。在缺乏I型IFN受体的小鼠的足垫或眼部感染后，HSV-1扩散到实质器官，包括肺、肝、脾和局部淋巴结，但小鼠存活。I型和II型IFN受体的缺失产生了数量上最大和最广泛的病毒传播到内脏器官和神经系统，这些小鼠在眼部或足垫感染后总是死亡。II型受体敲除小鼠和野生型小鼠具有相当的病毒复制和定位，没有HSV-1的全身传播或致死性。因此，虽然11型IFN受体的孤立缺陷并不影响发病机制，这些受体的损失与I型受体的遗传缺失相结合，对HSV-1的易感性产生了深远的影响。这些数据表明不同的影响，I型和II型干扰素在限制HSV-1的全身传播，并进一步验证使用生物发光成像的病毒发病机制的研究。
Herpes simplex virus type 1 (HSV-1) can produce disseminated, systemic infection in neonates and patients with AIDS or other immunocompromising diseases, resulting in significant morbidity and mortality in spite of antiviral therapy. Components of host immunity that normally limit HSV-1 to localized epithelial and neuronal infection remain incompletely defined. We used in vivo bioluminescence imaging to determine effects of type I and II interferons (IFNs) on replication and tropism of HSV-1 infection in mice with genetic deficiency of type I, type II, or both type I and II IFN receptors. Following footpad or ocular infection of mice lacking type I IFN receptors, HSV-1 spread to parenchymal organs, including lung, liver, spleen, and regional lymph nodes, but mice survived. Deletion of type I and II IFN receptors produced quantitatively greatest and most widespread dissemination of virus to visceral organs and the nervous system, and these mice invariably died after ocular or footpad infection. Type II receptor knockout and wild-type mice had comparable viral replication and localization, with no systemic spread of HSV-1 or lethality. Therefore, while isolated deficiency of type 11 IFN receptors did not affect pathogenesis, loss of these receptors in combination with genetic deletion of type I receptors had a profound effect on susceptibility to HSV-1. These data demonstrate different effects of type I and II IFNs in limiting systemic dissemination of HSV-1 and further validate the use of bioluminescence imaging for studies of viral pathogenesis.