No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank.

No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank.
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DOI:
10.1186/1756-0500-7-461
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发表时间:
2014-08-04
期刊:
影响因子:
1.8
通讯作者:
Gerondelis P
Gerondelis P
中科院分区:
其他
文献类型:
--
作者:
Irlbeck DM;Vernon SD;McCleary KK;Bateman L;Klimas NG;Lapp CW;Peterson DL;Brown JR;Remlinger KS;Wilfret DA;Gerondelis P

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2009年,一项回顾性研究报告了在慢性疲劳综合征或肌痛性脑脊髓炎(CFS)患者的临床分离株中检测到异嗜性小鼠白血病病毒相关病毒(XMRV)。虽然许多努力证实这一观察结果失败,但有一份报告检测到多嗜性小鼠白血病病毒(pMLV),而不是XMRV。在这两项研究中,采用了基于聚合酶链反应(PCR)的方法,这可以为开发实用的诊断工具提供基础。为了证实这些研究,我们假设检测这些病毒的能力不仅取决于所采用方法的技术细节,还取决于用于诊断CFS的标准和良好表征的临床分离株的可用性。通过从充分表征的CFS和健康受试者收集新鲜血液样本,生成来自地理上不同地点的临床分离株库。使用分子技术生成试验阳性对照,并确定鼠逆转录病毒和脑池内A颗粒(Cell 12(4):963-72,1977)检测方法的检测下限(LLOD)。我们报告建立了一个存储库的定义明确的,临床分离株从五个,地理上不同的地区,美国,比较确定的LLOD和验证工作,为以前报道的检测方法和结果的努力,以确认这些逆转录病毒的签名之间的关联,从个人CFS在一个盲态,多站点,前瞻性研究分离。我们检测到各种鼠逆转录病毒DNA特征,但无法解决CFS(5/72; 6.7%)和健康(2/37; 5.4%)受试者分离株之间检测发生率的差异(Fisher精确检验,p值= 1)。观察到的序列似乎反映了内源性鼠逆转录病毒DNA的检测,其与XMRV或pMLV不相同。我们无法证实先前报道的前瞻性多中心研究中XMRV或pMLV序列检测与CFS之间的相关性。检测到鼠逆转录病毒序列的频率较低,CFS和对照组之间没有差异。这些序列的性质似乎反映了所用PCR试剂中预先存在的内源性鼠逆转录病毒DNA的检测。
In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates. A repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods. We report the establishment of a repository of well-defined, clinical isolates from five, geographically distinct regions of the US, the comparative determination of the LLODs and validation efforts for the previously reported detection methods and the results of an effort to confirm the association of these retroviral signatures in isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher’s Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV. We were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed.