Contribution of viral mimics of cellular genes to KSHV infection and disease.

Contribution of viral mimics of cellular genes to KSHV infection and disease.
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DOI:
10.3390/v6093472
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发表时间:
2014-09-19
期刊:
Viruses
影响因子:
--
通讯作者:
Tosato G
Tosato G
中科院分区:
其他
文献类型:
--
作者:
Sakakibara S;Tosato G

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卡波西肉瘤相关疱疹病毒(KSHV,也被称为人类疱疹病毒8 HHV-8)是卡波西肉瘤(KS)的病因,卡波西肉瘤是全世界hiv感染者中最常见的恶性肿瘤,原发性积液性淋巴瘤(PEL)和多中心Castleman病(MCD)。KSHV是一种双链DNA病毒,可编码细胞蛋白的几种同源物。病毒和宿主蛋白之间的结构相似性解释了为什么一些病毒同源物作为它们的宿主对应物起作用,但有时在不寻常的解剖位点和不适当的时间。在其他情况下,病毒蛋白的结构修饰可以抑制或覆盖宿主同源物的功能,从而导致kshv相关疾病。例如,病毒IL-6 (vIL-6)与人类IL-6完全不同,可以独立于α亚基激活gp130信号。因此,IL-6可以激活许多对细胞IL-6无反应的细胞类型,从而导致MCD疾病的表现。在这里,我们讨论了作为病毒/宿主相互作用通道的细胞产物的KSHV同源物的分子生物学,重点是确定治疗KS和其他KSHV相关疾病的新策略。
Kaposi’s sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6) is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases.
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