Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies.
Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies.
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DOI：
10.1186/1742-4690-7-68
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发表时间：
2010-08-17
期刊：
影响因子：
3.3
通讯作者：
Hackett J Jr
中科院分区：
文献类型：
--
作者：
Qiu X;Swanson P;Luk KC;Tu B;Villinger F;Das Gupta J;Silverman RH;Klein EA;Devare S;Schochetman G;Hackett J Jr
异嗜性鼠白血病病毒相关病毒（XMRV）是最近在前列腺癌组织和慢性疲劳综合征患者的淋巴细胞中发现的一种人γ逆转录病毒。要确定 XMRV 感染在人类疾病中的病因学作用，需要大规模的流行病学研究。开发 XMRV 特异性抗体检测方法将极大地促进此类研究。然而，针对 XMRV 感染的抗体反应的性质和动力学尚未确定。三只恒河猴感染了 XMRV，以确定 XMRV 感染引起的抗体反应的动态。所有猕猴在感染第二周都产生了针对 XMRV 的抗体，主要反应是针对包膜蛋白 gp70、跨膜蛋白 p15E 和衣壳蛋白 p30。一般来说，针对 gp70 和 p15E 的抗体反应比针对 p30 的抗体反应出现得更早，滴度更高，尤其是在血清转化的早期。 gp70、p15E 和 p30 的抗体持续长达 158 天，并因再次感染而大幅增强，因此被认为是有用的血清学标志物。使用重组蛋白开发了三种高通量原型测定法来检测这些病毒蛋白的抗体。通过检测来自 XMRV 感染的猕猴的所有蛋白质印迹 (WB) 阳性连续出血，gp70 和 p15E 原型检测均显示出 100% 的灵敏度，并且对献血者具有良好的特异性 (99.5-99.9%)。 p30 原型测定的血清转换敏感性和特异性分别为 92% 和 99.4%。这项研究首次证明了 XMRV 感染引起的血清转化模式。灵长类动物对 XMRV 抗体反应的性质和动力学已得到充分表征。此外，还确定了可用于检测 XMRV 感染的关键血清学标志物。开发了三种原型免疫测定法来检测 XMRV 特异性抗体。这些检测方法表现出良好的敏感性和特异性；因此，它们将促进人类 XMRV 感染的大规模流行病学研究。
Xenotropic Murine Leukemia Virus-related Virus (XMRV) is a human gammaretrovirus recently identified in prostate cancer tissue and in lymphocytes of patients with chronic fatigue syndrome. To establish the etiologic role of XMRV infection in human disease requires large scale epidemiologic studies. Development of assays to detect XMRV-specific antibodies would greatly facilitate such studies. However, the nature and kinetics of the antibody response to XMRV infection have yet to be determined. Three rhesus macaques were infected with XMRV to determine the dynamics of the antibody responses elicited by infection with XMRV. All macaques developed antibodies to XMRV during the second week of infection, and the predominant responses were to the envelope protein gp70, transmembrane protein p15E, and capsid protein p30. In general, antibody responses to gp70 and p15E appeared early with higher titers than to p30, especially in the early period of seroconversion. Antibodies to gp70, p15E and p30 persisted to 158 days and were substantially boosted by re-infection, thus, were identified as useful serologic markers. Three high-throughput prototype assays were developed using recombinant proteins to detect antibodies to these viral proteins. Both gp70 and p15E prototype assays demonstrated 100% sensitivity by detecting all Western blot (WB) positive serial bleeds from the XMRV-infected macaques and good specificity (99.5-99.9%) with blood donors. Seroconversion sensitivity and specificity of the p30 prototype assay were 92% and 99.4% respectively. This study provides the first demonstration of seroconversion patterns elicited by XMRV infection. The nature and kinetics of antibody responses to XMRV in primates were fully characterized. Moreover, key serologic markers useful for detection of XMRV infection were identified. Three prototype immunoassays were developed to detect XMRV-specific antibodies. These assays demonstrated good sensitivity and specificity; thus, they will facilitate large scale epidemiologic studies of XMRV infection in humans.
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影响因子：
3.7
作者：
Erlwein O;Kaye S;McClure MO;Weber J;Wills G;Collier D;Wessely S;Cleare A
通讯作者：
Cleare A
影响因子：
3.3
作者：
Groom HC;Boucherit VC;Makinson K;Randal E;Baptista S;Hagan S;Gow JW;Mattes FM;Breuer J;Kerr JR;Stoye JP;Bishop KN
通讯作者：
Bishop KN
影响因子：
56.9
作者：
Lombardi, Vincent C.;Ruscetti, Francis W.;Mikovits, Judy A.
通讯作者：
Mikovits, Judy A.
影响因子：
5.4
作者：
Rodriguez, Jason J.;Goff, Stephen P.
通讯作者：
Goff, Stephen P.
影响因子：
2.1
作者：
Arnold, Rebecca S.;Makarova, Natalia V.;Petros, John A.
通讯作者：
Petros, John A.