Quantification of Human Herpesvirus 6 in Immunocompetent Persons and Post-mortem Tissues from AIDS Patients by PCR

Clark, Duncan A.; Ait‐Khaled, Mounir; Wheeler, A C; Kidd, IM; McLaughlin, James E.; Ma, Jun; Griffiths, Paul; Emery, Vincent

doi:10.1099/0022-1317-77-9-2271

Cited by 85 publications

(61 citation statements)

References 23 publications

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“…Since normal CSF, i.e., in the absence of inflammation, contains a few leukocytes, it is only to be expected that, in cases of HHV-6 integration, viral DNA will be present in CSF even though there is no viral replication. This is in sharp contrast to the usual scenario in immunocompetent persons in whom, after primary infection, HHV-6 persists throughout life and is only found in the infrequent leukocyte (7), and hence, viral DNA is not normally found in CSF.…”

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confidence: 77%

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

et al. 2007

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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. HHV-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 10 copies/ml). The prevalences of CSF HHV-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 HHV-6B. 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.

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confidence: 77%

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

et al. 2007

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“…The same is true for the detection of HHV-6 DNA by PCR in peripheral blood mononuclear cells (PBMCs), the site where the virus establishes latency. In these cases, HHV-6 DNA can be detected by PCR in PBMCs at low levels (9). Viral culture is a difficult and time-consuming process and is not routinely used in clinical laboratories to detect virus in CSF specimens.…”

Section: Discussionmentioning

confidence: 99%

Detection and Typing of Human Herpesvirus 6 by Molecular Methods in Specimens from Patients Diagnosed with Encephalitis or Meningitis

et al. 2007

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Human herpesvirus 6 (HHV-6) was detected in specimens from patients hospitalized with symptoms of encephalitis or meningitis. A real-time PCR assay was developed which has a linear dynamic range of 5 to 5 ؋ 10 6 copies of HHV-6 and a sensitivity of five gene copies per reaction. While the assay detects both subtypes, HHV-6A and HHV-6B, it is specific and does not cross-react with a selected specificity panel. A total of 1,482 patient specimens, which were collected between 2003 and 2007, were tested; 26 specimens from 24 patients were found to be positive for HHV-6 by real-time PCR. The HHV-6 detection rate in this population was therefore 1.75%. The majority of the specimens tested (>95%) were cerebrospinal fluid (CSF) specimens. We were able to type 20 of the 26 positive specimens by conventional PCR and sequence analysis; all were HHV-6B. Forty-two percent of the patients were 3 years of age or younger, which may indicate a primary infection in these patients. Given the ages of the remaining patients (from 4 to 81 years), their infections were most probably due to virus reactivations. Where information was available, symptoms of patients included fever (71%), altered mental status (67%), and abnormal CSF profile (75%). Fifty percent of patients of 3 years of age or younger suffered from seizures. The detection of HHV-6 in specimens from patients diagnosed with encephalitis or meningitis, in the absence of a positive PCR result for other agents, strongly suggests a role for HHV-6 in the pathogenesis of these central nervous system diseases.

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“…HHV-6 DNA was quantified by a previously described competitive technique. 6,22 This nested PCR amplifies the same region as the qualitative PCR assay and has a broad dynamic range with a lower limit of accurate quantification of 10 genome copies.…”

Section: Pcr Methodsmentioning

confidence: 99%

Human herpesvirus 6 infection and cytomegalovirus-specific lymphoproliferative responses in allogeneic stem cell transplant recipients

Larsson

Linde

et al. 2002

Bone Marrow Transplant

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Summary:The aim of this study was to investigate the effects of HHV-6 DNAemia on the CMV specific lymphoproliferative response after allogeneic stem cell transplantation. Twenty-one allogeneic stem cell transplantation (allo-SCT) patients were included in the study. The patients were either CMV seropositive and/or had CMV seropositive donors. We studied the effects of HHV-6 infection, documented by PCR, on CMV-specific lymphocyte proliferation response and on CMV infection documented by PCR. HHV-6 DNAemia correlated with the absence of CMV-specific lymphocyte proliferation responses after allo-SCT. Three of nine patients with persistent HHV-6 DNA had a CMV-specific lymphocyte proliferative response compared to 11 of 12 patients without persistent HHV-6 DNAemia (P = 0.02). Patients with higher HHV-6 DNA levels (Ͼ100 copies) were more likely than those with lower copy numbers not to develop a CMV-specific immune response (six of nine vs one of eight; P Ͻ 0.05). Patients who were repeatedly HHV-6 positive in three or more consecutive blood samples were also more likely to need repeated courses of preemptive antiviral therapy against CMV during the first 6 months after transplantation (P Ͻ 0.001). Our data indicate the possibility that HHV-6 can suppress the development of CMV-specific immune responses and thereby could predispose to development of late CMV disease.

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Quantification of Human Herpesvirus 6 in Immunocompetent Persons and Post-mortem Tissues from AIDS Patients by PCR

Cited by 85 publications

References 23 publications

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

Detection and Typing of Human Herpesvirus 6 by Molecular Methods in Specimens from Patients Diagnosed with Encephalitis or Meningitis

Human herpesvirus 6 infection and cytomegalovirus-specific lymphoproliferative responses in allogeneic stem cell transplant recipients

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