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北美汉坦病毒——黑溪运河病毒在实验性感染刚毛棉鼠中的发病机制

Pathogenesis of a North American hantavirus, Black Creek Canal virus, in experimentally infected Sigmodon hispidus.

作者信息

Hutchinson K L, Rollin P E, Peters C J

机构信息

Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

出版信息

Am J Trop Med Hyg. 1998 Jul;59(1):58-65. doi: 10.4269/ajtmh.1998.59.58.

DOI:10.4269/ajtmh.1998.59.58
PMID:9684629
Abstract

This report describes the first detailed analysis of the replication, persistence, and excretion of a North American hantavirus in its natural rodent reservoir. Black Creek Canal virus was isolated from Sigmodon hispidus (cotton rat) shortly after the identification of a hantavirus pulmonary syndrome (HPS) case occurring in southern Florida. Six-week-old male cotton rats were inoculated subcutaneously with 1,000 tissue culture infectious doses. Viral complementary RNA (vcRNA) was quantified as a means of determining the site(s) of viral activity (transcription and replication). In the first few weeks post inoculation (pi), vcRNA was detectable in every tissue examined except blood. The quantities of vcRNA decreased over time, and by five months pi it could be detected only in the brain. In addition to using a quantitative polymerase chain reaction (QPCR) as a means of measuring viral replication/transcription, attempts were made to reisolate virus from all tissue samples taken. Virus could be isolated from every solid tissue examined, and the titers appeared to decrease over time, similar to the QPCR results. However, in contrast to the QPCR results, infectious virus was still routinely detectable at low levels in adrenal gland, liver, kidney, and testicle 150 days pi. Although results of testing for vcRNA in the blood were uniformly negative, infectious virus was detected at one week pi, reached highest titers at two weeks, and decreased dramatically by three weeks. After three weeks pi, infectious virus could only be detected sporadically in blood. Virus was isolated from urine collected during the first 70 days pi and throughout the entire study period in feces and wet bedding. These data indicate that the viral infection can be separated into an acute phase associated with high virus titers, and a chronic or persistent phase associated with lower virus titers and continued shedding of virus in excreta.

摘要

本报告描述了对一种北美汉坦病毒在其天然啮齿动物宿主中的复制、持续存在和排泄情况的首次详细分析。在佛罗里达州南部确诊一例汉坦病毒肺综合征(HPS)病例后不久,从棉鼠中分离出了黑溪运河病毒。六周龄雄性棉鼠皮下接种1000个组织培养感染剂量。病毒互补RNA(vcRNA)被定量,作为确定病毒活性位点(转录和复制)的一种手段。在接种后的最初几周内,除血液外,在检查的每个组织中都可检测到vcRNA。vcRNA的量随时间减少,到接种后五个月,仅在脑中可检测到。除了使用定量聚合酶链反应(QPCR)作为测量病毒复制/转录的手段外,还尝试从采集的所有组织样本中重新分离病毒。可以从检查的每个实体组织中分离出病毒,并且滴度似乎随时间下降,与QPCR结果相似。然而与QPCR结果相反,在接种后150天,肾上腺、肝脏、肾脏和睾丸中仍可常规检测到低水平的感染性病毒。尽管血液中vcRNA检测结果均为阴性,但在接种后一周检测到感染性病毒,在两周时达到最高滴度,三周时急剧下降。接种后三周后,仅偶尔在血液中检测到感染性病毒。在接种后前70天收集到的尿液以及整个研究期间的粪便和潮湿垫料中均分离出病毒。这些数据表明,病毒感染可分为与高病毒滴度相关的急性期和与低病毒滴度及排泄物中持续排出病毒相关的慢性或持续期。

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