Fibrils of Prostatic Acid Phosphatase Fragments Boost Infections with XMRV (Xenotropic Murine Leukemia Virus-Related Virus), a Human Retrovirus Associated with Prostate Cancer

Fibrils of Prostatic Acid Phosphatase Fragments Boost Infections with XMRV (Xenotropic Murine Leukemia Virus-Related Virus), a Human Retrovirus Associated with Prostate Cancer
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DOI:
10.1128/jvi.00268-09
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发表时间:
2009-07-15
影响因子:
5.4
通讯作者:
Silverman, Robert H.
Silverman, Robert H.
中科院分区:
医学2区
文献类型:
--
作者:
Hong, Seunghee;Klein, Eric A.;Silverman, Robert H.

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异嗜性小鼠白血病病毒相关病毒(XMRV)最近在前列腺癌组织中被检测到,并可能在肿瘤发生中起作用。目前还不清楚这种病毒是如何传播的,以及哪些因素促进了它在前列腺中的传播。我们发现,源自前列腺酸性磷酸酶的淀粉样蛋白片段,即精液源性病毒感染增强子(SEVI),极大地增加了原发前列腺上皮细胞和基质细胞的XMRV感染。用XMRV包膜蛋白假型的猿猴/人类免疫缺陷嵌合病毒颗粒证明,SEVI或人类精液本身的增强作用是在病毒附着和进入的水平上。SEVI增强了XMRV的传染性,但没有绕过对异向性和多向性逆转录病毒受体1的要求。此外,在一些前列腺癌患者的前列腺分泌物中检测到XMRV RNA。前列腺大量产生SEVI前体的事实表明,XMRV复制发生在提供病毒感染自然增强剂的环境中,这可能在该病毒在人群中的传播中发挥作用。
The xenotropic murine leukemia virus-related virus (XMRV) has recently been detected in prostate cancer tissues and may play a role in tumorigenesis. It is currently unclear how this virus is transmitted and which factors promote its spread in the prostate. We show that amyloidogenic fragments known as semen-derived enhancer of virus infection (SEVI) originating from prostatic acid phosphatase greatly increase XMRV infections of primary prostatic epithelial and stromal cells. Hybrid simian/human immunodeficiency chimeric virus particles pseudotyped with XMRV envelope protein were used to demonstrate that the enhancing effect of SEVI, or of human semen itself, was at the level of viral attachment and entry. SEVI enhanced XMRV infectivity but did not bypass the requirement for the xenotropic and polytropic retrovirus receptor 1. Furthermore, XMRV RNA was detected in prostatic secretions of some men with prostate cancer. The fact that the precursor of SEVI is produced in abundance by the prostate indicates that XMRV replication occurs in an environment that provides a natural enhancer of viral infection, and this may play a role in the spread of this virus in the human population.