Case of fatal encephalitis by HHV‐6 variant A

Portolani, Marinella; Pecorari, Monica; Tamassia, Maria Grazia; Gennari, William; Beretti, Francesca; Guaraldi, Giovanni

doi:10.1002/jmv.2012

Cited by 32 publications

(24 citation statements)

References 22 publications

(19 reference statements)

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“…There are a remarkable number of cases of encephalitis in immunocompetent adults attributed to variant A, 6 in all (4,13,26,29,30,39), as opposed to one attributed to variant B (5,28). As previously discussed, HHV-6B, not HHV-6A, is responsible for primary infection in childhood, whereas either variant A or B can be integrated into human chromosomes.…”

Section: Discussionmentioning

confidence: 88%

“…Turning to older individuals in whom primary infection is extremely unlikely, there are a few case reports describing, in all, 11 immunocompetent adults and 1 teenager. All had clinically defined encephalitis and HHV-6 DNA in their CSF (4,5,13,21,26,29,30,33,39), and in each case, the diagnosis was given as HHV-6 encephalitis but viral integration had not been considered. Viral DNA load in CSF was measured in 7 patients; low level HHV-6 DNA was found in 2 of these but in both primary infection was excluded (29,30) suggesting viral reactivation.…”

Section: Discussionmentioning

confidence: 99%

“…All had clinically defined encephalitis and HHV-6 DNA in their CSF (4,5,13,21,26,29,30,33,39), and in each case, the diagnosis was given as HHV-6 encephalitis but viral integration had not been considered. Viral DNA load in CSF was measured in 7 patients; low level HHV-6 DNA was found in 2 of these but in both primary infection was excluded (29,30) suggesting viral reactivation. The remaining 5 had high viral DNA levels (Ն4.0 log 10 copies/ml) (5, 21), which although not noted in the reports, is equivalent to at least 1 viral copy/CSF leukocyte, strongly suggesting chromosomal HHV-6 integration.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Based on evidence that the ST C variant is the most susceptible to HHV-6A of the ST isoforms we tested, we propose that the predominant expression of ST C in the brain is related to the high sensitivity of the brain to HHV-6-mediated encephalitis. In fact, fatal encephalitis cases that were caused by HHV-6A have been reported (28,42).…”

Section: Fig 5 Hhv-6b-induced Polykaryocytes In Mt4 Cells Hsb-2 Cementioning

confidence: 99%

Human Herpesvirus 6 Variant A but Not Variant B Induces Fusion from Without in a Variety of Human Cells through a Human Herpesvirus 6 Entry Receptor, CD46

Mori

Seya

Huang

et al. 2002

J Virol

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Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus that productively infects T cells and monocytes. HHV-6 isolates can be differentiated into two groups, variants A and B (HHV-6A and HHV-6B). Here, we show a functional difference between HHV-6A and -6B in that HHV-6A induced syncytium formation of diverse human cells but HHV-6B did not. The syncytium formation induced by HHV-6A was observed 2 h after infection; moreover, it was found in the presence of cycloheximide, indicating that HHV-6A induced fusion from without (FFWO) in the target cells. Furthermore, the fusion event was dependent on the expression of the HHV-6 entry receptor, CD46, on the target cell membrane. In addition, we determined that short consensus repeat 2 (SCR2), -3, and -4 of the CD46 ectodomain were essential for the formation of the virus-induced syncytia. Monoclonal antibodies against glycoproteins B and H of HHV-6A inhibited the fusion event, indicating that the syncytium formation induced by HHV-6A required glycoproteins H and B. These findings suggest that FFWO, which HHV-6A induced in a variety of cell lines, may play an important role in the pathogenesis of HHV-6A, not only in lymphocytes but also in various tissues, because CD46 is expressed ubiquitously in human tissues.

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“…However, quite recently, HHV-6A and HHV-6B were reclassified into different species (according to the Virus Taxonomy List 2011). HHV-6B is the causative agent of exanthem subitum (6) and mainly causes reactivation in immunocompromised hosts (7,8), while HHV-6A is involved in the etiology of several diseases, including multiple sclerosis (9), encephalitis (10), and Hashimoto's thyroiditis (11). Almost all children have antibodies against HHV-6A or HHV-6B by 2 years of age (12).…”

mentioning

confidence: 99%

Identification of the Human Herpesvirus 6A gQ1 Domain Essential for Its Functional Conformation

Maeki

Hayashi

Kawabata

et al. 2013

J Virol

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cHuman herpesvirus 6 is a T lymphotropic herpesvirus, long classified into variants A and B (HHV-6A and HHV-6B) based on differences in sequence and pathogenicity. Recently, however, HHV-6A and HHV-6B were reclassified as different species. Here, we isolated a neutralizing monoclonal antibody (Mab) named AgQ 1-1 that was specific for HHV-6A glycoprotein Q1 (AgQ1), and we showed that amino acid residues 494 to 497 of AgQ1 were critical for its recognition by this Mab. This region was also essential for AgQ1's complex formation with gH, gL, and gQ2, which might be important for viral binding to the cellular receptor, CD46. In addition, amino acid residues 494 to 497 are essential for viral replication. Interestingly, this sequence corresponds to the domain on HHV-6B gQ1 that is critical for recognition by an HHV-6B-specific neutralizing Mab. Within this domain, only Q at position 496 of HHV-6A is distinct from the HHV-6B sequence; however, the mutant AgQ1(Q496E) was still clearly recognized by the Mab AgQ 1-1. Surprisingly, replacement of the adjacent amino acid, in mutant AgQ1(C495A), resulted in poor recognition by Mab AgQ 1-1, and AgQ1(C495A) could not form the gH/gL/gQ1/gQ2 complex. Furthermore, the binding ability of mutant AgQ1(L494A) with CD46 decreased, although it could form the gH/gL/gQ1/gQ2 complex and it showed clear reactivity to Mab AgQ 1-1. These data indicated that amino acid residues 494 to 497 of AgQ1 were critical for the recognition by Mab AgQ 1-1 and essential for AgQ1's functional conformation.

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Case of fatal encephalitis by HHV‐6 variant A

Cited by 32 publications

References 22 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

Human Herpesvirus 6 Variant A but Not Variant B Induces Fusion from Without in a Variety of Human Cells through a Human Herpesvirus 6 Entry Receptor, CD46

Identification of the Human Herpesvirus 6A gQ1 Domain Essential for Its Functional Conformation

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