Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis

Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis
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DOI:
10.1128/jcm.02115-06
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发表时间:
2007-04-01
影响因子:
9.4
通讯作者:
Clark, Duncan A.
Clark, Duncan A.
中科院分区:
医学2区
文献类型:
--
作者:
Ward, Katherine N.;Leong, Hoe Nam;Clark, Duncan A.

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本文比较了人类疱疹病毒6型(HHV-6)DNA在免疫功能正常的原发感染者和病毒染色体整合者脑脊液(CSF)中的检出率和浓度。对510名疑似脑炎患者、200名幼儿和310名年龄较大的儿童和/或成人以及12名其他患者的样本进行了检测。使用PCR测量CSF、血清和全血中的HRV-6 DNA浓度(log(10)拷贝/ml)。间接免疫荧光法测定血清HHV-6 IgG抗体。原发感染定义为抗体血清转换和/或血清阴性血清中HHV-6 DNA浓度低(< 3.0 log(10)copies/ml)。染色体整合定义为血清(>= 3.5 log(10)拷贝/ml)或全血(>= 6.0 log,0拷贝/ml)中病毒DNA的高浓度。脑脊液HRV-6 DNA在原发感染和染色体整合中的检出率在幼儿(< 2岁)中分别为2.5%和2.0%,在大龄儿童和/或成人中分别为0%和1.3%。9例原发感染患儿脑脊液HHV-6 DNA平均浓度(2.4 log(10)copies/ml)明显低于21例病毒染色体整合患儿(4.0 log(10)copies/ml)。在原发感染中仅发现HHV-6 B DNA,而在病毒整合中,4例患者具有HHV-6A,17例患者具有HIIV-B3。除了原发感染外,染色体整合是免疫活性者CSF中HHV-6 DNA最可能的原因。我们的研究结果表明,任何HHV-6脑炎或其他类型的活动性中枢神经系统感染的诊断,不应该首先排除染色体HHV-6整合通过测量CSF,血清和/或全血中的DNA负荷。
The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HRV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6 immunoglobulin G antibody was measured by indirect immunofluorescence. Primary infection was defined by antibody seroconversion and/or a low concentration of HHV-6 DNA (< 3.0 log(10) copies/ml) in a seronegative serum. Chromosomal integration was defined by a high concentration of viral DNA in serum (>= 3.5 log(10) copies/ml) or whole blood (>= 6.0 log,0 copies/ml). The prevalences of CSF HRV-6 DNA in primary infection and chromosomal integration were 2.5% and 2.0%, respectively, in the young children (< 2 years) and 0% and 1.3%, respectively, in the older children and/or adults. The mean concentration of CSF HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was significantly lower than that of 21 patients with viral chromosomal integration (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas in viral integration, 4 patients had HHV-6A and 17 patients HIIV-B3. Apart from primary infection, chromosomal integration is the most likely cause of HHV-6 DNA in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6 encephalitis or other type of active central nervous system infection should not be made without first excluding chromosomal HHV-6 integration by measuring DNA load in CSF, serum, and/or whole blood.