Production by gamma interferon in BCBL-1 inhibition of infectious human herpesvirus 8 interferon and α cells
Production by gamma interferon in BCBL-1 inhibition of infectious human herpesvirus 8 interferon and α cells
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DOI：
10.1099/vir.0.80214-0
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发表时间：
2004-10-01
影响因子：
3.8
通讯作者：
Offermann, MK
中科院分区：
文献类型：
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作者：
Pozharskaya, VP;Weakland, LL;Offermann, MK
人类疱疹病毒-8(HHV-8)与卡波西肉瘤和原发渗出性淋巴瘤有关。虽然干扰素-α和干扰素-γ都是抗病毒细胞因子，但干扰素-α可以阻止HHV-8进入裂解期，而干扰素-伽马能诱导进行裂解复制的细胞百分比增加。必须完成裂解级联反应中的多个事件才能产生传染性病毒。探讨两种类型的干扰素对感染性病毒产生的影响。干扰素-α和干扰素-γ均可诱导HHV-8感染的BCBL-1细胞表达抗病毒蛋白双链RNA活化蛋白激酶(PKR)和2‘5’-寡腺苷合成酶(2‘5’-OAS)。与干扰素-α孵育产生的IRF-1水平高于与干扰素-γ孵育的水平，而干扰素-γ诱导的IRF-1水平高于干扰素-α。干扰素-γ诱导的裂解病毒基因表达略有增加，而感染性病毒的表达没有明显增加。当用TPA诱导HHV-8裂解复制时，条件培养液中出现高水平的感染性病毒。当TPA刺激过程中存在干扰素-γ时，感染性病毒的产生至少减少了60%，并且干扰素-α完全阻断了TPA诱导的感染性病毒的产生。干扰素-α对病毒产量的显著抑制与干扰素-α诱导的抗病毒蛋白PKR和2‘5’-OAS水平高于干扰素-γ相一致。这些研究表明，尽管干扰素-γ诱导一些细胞进入HHV-8复制的裂解阶段，但干扰素-γ增强了细胞的抗病毒防御能力，足以防止感染病毒的产生。
Human herpesvirus-8 (HHV-8) is aetiologically linked to Kaposi's sarcoma and primary effusion lymphoma. Although interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) are both antiviral cytokines, IFN-alpha blocks entry of HHV-8 into the lytic phase, whereas IFN-gamma induces an increase in the percentage of cells undergoing lytic replication. Multiple events in the lytic cascade must be completed to produce infectious virus. The ability of both types of IFN to affect the production of infectious virus was explored. Both IFN-alpha and IFN-gamma induced expression of the antiviral proteins double-stranded RNA-activated protein kinase (PKR) and 2'5'-oligoadenylate synthetase (2'5'-OAS) in HHV-8-infected BCBL-1 cells. Higher levels resulted from incubation with IFN-alpha than with IFN-gamma, whereas IFN-gamma induced higher levels of IRF-1 than did IFN-alpha. IFN-gamma induced a minor increase in lytic viral gene expression, which was not accompanied by a detectible increase in infectious virus. When lytic replication of HHV-8 was induced using TPA, high levels of infectious virus appeared in the conditioned medium. When IFN-gamma was present during TPA stimulation, the production of infectious virus was reduced by at least a 60 %, and IFN-alpha fully blocked TPA-induced production of infectious virus. The greater reduction of viral production that occurred with IFN-alpha is consistent with the higher levels of the antiviral proteins PKR and 2'5'-OAS induced by IFN-alpha than by IFN-gamma. These studies indicate that the augmentation of cellular antiviral defences by IFN-gamma was sufficient to prevent production of infectious virus despite IFN-gamma-induced entry of some cells into the lytic phase of HHV-8 replication.