Science被撤论文再起争议 华裔教授提出新观点

9月18日，PLoS Pathogens 杂志也撤销的一篇关于XMRV病毒的论文，而同一天PLoS ONE杂志又发布了一项新研究，文章作者是加州大学旧金山分校华裔教授Charles Chiu，新论文主要通过深入分析，指出没有证据表明前列腺癌中出现了XMRV病毒感染。

　　生物通报道：去年关于一种称为异嗜性小鼠白血病病毒相关病毒(Xenotropic murine leukemia virus-related virus)——XMRV病毒的研究成果引发了众多围观，美国国家癌症研究所提出了同一研究所的另外一项研究有问题，之后Science杂志撤销了这篇有关XMRV病毒与慢性疲劳综合症的论文部分内容。

9月18日，PLoS Pathogens 杂志也撤销的一篇关于XMRV病毒的论文，该杂志的编辑提出了撤销，这令这项2006年论文的作者感到错愕，这篇论文主要报道了XMRV与前列腺癌之间的联系。作者没有想到论文会被撤销，而且杂志也没有征求或通知相关事宜。

而同一天PLoS ONE杂志又发布了一项新研究，文章作者是加州大学旧金山分校华裔教授Charles Chiu，新论文主要通过深入分析，指出没有证据表明前列腺癌中出现了XMRV病毒感染。

前面要求被退回论文的部分作者也参与了这项研究，他们认为2006年的研究结果并不成立，正在深入调查之前实验室出现了什么问题，“但是关于XMRV病毒这种新病毒的发现，仍然成立，”作者之一，美国俄亥俄州克利夫兰诊所 Robert Silverman说，撤销前列腺癌与XMRV病毒之间的联系就行了。

Chiu教授表示，论文作者为其之前未主动撤销论文付出了代价，其他几份比PLoS ONE影响因子更高的期刊曾同意发表论文，条件是作者要撤回2006年的研究，但这一团队拒绝了，Chiu说（Chiu未参与前研究）。

XMRV与前列腺癌之间的可能联系是XMRV的故事中为数不多还在延续的内容，9月18日，mBIO杂志公布了一项大型多研究机构参与发布的研究成果，这一研究再次证实XMRV，或一组相关的病毒与CFS之间没有关联。之前Science杂志的相关报道已被退回，2010年PNAS杂志的研究内容也是如此。

在最新的这项研究中，Chiu教授与Silverman等人分析了39个新的前列腺癌患者的肿瘤样本，采用三种不同的技术研究XMRV，他们也找回了2006年研究中的肿瘤组织。这一次，他们在任何样本并没有发现XMRV，不过在2006年的保存RNA提取物中却发现了病毒，这表明之前样品处理过程中可能发生污染。

进一步的研究采用了一些新技术，表明该病毒来自LNCaP，这是一种感染了XMRV的细胞系，Silverman实验室之前曾用于其他研究中。 LNCaP细胞系，反过来被22Rv1污染，后者是另一种广泛使用的，含有XMRV的细胞系。

这项新研究由于其为澄清事实不断努力而受到褒奖，“这篇论文令我为这些作者和专业性而感到自豪，”美国癌症研究所，前XMRV研究人员Vinay Pathak 说，“这些科学家没有考虑个人得失，积极不懈地进行多方调查，追求真相。”，这个金团队都应“获得一枚奖章”，CFIDS协会负责人Kim McCleary补充说，在漫长的将CFS疾病错误归因为这个病原体的时间里，McCleary说她从来没有见到科学家们退缩过。

（生物通：张迪）

原文摘要：

In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer

XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection.

Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant

Ribonuclease L (RNase L) is an important effector of the innate antiviral response. Mutations or variants that impair function of RNase L, particularly R462Q, have been proposed as susceptibility factors for prostate cancer. Given the role of this gene in viral defense, we sought to explore the possibility that a viral infection might contribute to prostate cancer in individuals harboring the R462Q variant. A viral detection DNA microarray composed of oligonucleotides corresponding to the most conserved sequences of all known viruses identified the presence of gammaretroviral sequences in cDNA samples from seven of 11 R462Q-homozygous (QQ) cases, and in one of eight heterozygous (RQ) and homozygous wild-type (RR) cases. An expanded survey of 86 tumors by specific RT-PCR detected the virus in eight of 20 QQ cases (40%), compared with only one sample (1.5%) among 66 RQ and RR cases. The full-length viral genome was cloned and sequenced independently from three positive QQ cases. The virus, named XMRV, is closely related to xenotropic murine leukemia viruses (MuLVs), but its sequence is clearly distinct from all known members of this group. Comparison of gag and pol sequences from different tumor isolates suggested infection with the same virus in all cases, yet sequence variation was consistent with the infections being independently acquired. Analysis of prostate tissues from XMRV-positive cases by in situ hybridization and immunohistochemistry showed that XMRV nucleic acid and protein can be detected in about 1% of stromal cells, predominantly fibroblasts and hematopoietic elements in regions adjacent to the carcinoma. These data provide to our knowledge the first demonstration that xenotropic MuLV-related viruses can produce an authentic human infection, and strongly implicate RNase L activity in the prevention or clearance of infection in vivo. These findings also raise questions about the possible relationship between exogenous infection and cancer development in genetically susceptible individuals.