Detection of human herpesvirus‐6 in cerebrospinal fluid of patients with encephalitis

Yao, Karen; Honarmand, Somayeh; Espinosa, Alex; Akhyani, Nahid; Glaser, Carol; Jacobson, Steven

doi:10.1002/ana.21611

Cited by 94 publications

(72 citation statements)

References 44 publications

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“…Quantitative PCR assays are not standardized and the output can vary significantly depending on factors such as the extraction method used, calibration and so on. 53,54 A limitation of this analysis is the inability to conclusively exclude from the analysis patients with ciHHV-6 based only on reported plasma PCR values. Less than 1% (estimates range from 0.2 to 0.85%) of the population is born with ciHHV-6; these individuals will always test positive for HHV-6 in whole blood and serum, and usually will test positive in plasma and CSF-even when the virus is not actively replicating-due to natural cell breakdown in the circulation.…”

Section: Discussionmentioning

confidence: 99%

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Scheurer

Pritchett

Amirian

et al. 2012

Bone Marrow Transplant

108

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Reactivation of human herpesvirus-6 (HHV-6) frequently occurs following hematopoietic SCT (HSCT), and has been associated with clinical consequences in many patient populations. HHV-6 reactivation and HHV-6 encephalitis seem to occur more frequently in patients undergoing HSCT with cord blood (CB) as the stem cell source. We have conducted a systematic literature review and meta-analysis to investigate the clinical significance of this correlation. A systematic review of publications indexed in PubMed was performed for HSCT studies published over the past 10 years that fit inclusion criteria. Data on prevalences of HHV-6 reactivation and HHV-6 encephalitis post HSCT were abstracted from 19 papers. Meta-analyses were conducted to calculate combined prevalence estimates. The prevalences of HHV-6 reactivation and encephalitis were compared among CB vs non-CB HSCT. Prevalences of HHV-6 reactivation and HHV-6 encephalitis were significantly higher in patients receiving CB as the stem cell source than in patients receiving another stem cell source (72.0% vs 37.4%, Po0.0001; 8.3% vs 0.50%, Po0.0001, respectively). HHV-6 reactivation and HHV-6 encephalitis are significant complications in the post-HSCT setting, particularly in patients receiving CB as the stem cell source. Thus, patients undergoing umbilical CB transplantation should be closely monitored for HHV-6 reactivation.

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Section: Discussionmentioning

confidence: 99%

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Scheurer

Pritchett

Amirian

et al. 2012

Bone Marrow Transplant

108

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“…In this situation, it is admitted that the value of viremia does not need to be significantly high to establish the diagnosis of active infection. Accordingly, due to the sensitivity and specificity of current PCR techniques, the detection of HHV-6 DNA in CSF is considered sufficient for the diagnosis of an active infection of the CNS, regardless of the level of viremia (135,136). This raises the question of possible restricted local reactivations in the CNS, as suggested in some cases for HHV-6 encephalitis after HSCT (137,138).…”

Section: Active Infectionmentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.

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“…Both HHV-6A and -6B are neurotropic, and both viruses have been linked to diseases of the central nervous system, such as encephalitis (48). In addition, evidence exists for an association between HHV-6B and mesial temporal lobe epilepsy (10,11).…”

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confidence: 99%

U20 Is Responsible for Human Herpesvirus 6B Inhibition of Tumor Necrosis Factor Receptor-Dependent Signaling and Apoptosis

Kofod-Olsen

Ross‐Hansen

Schleimann

et al. 2012

J Virol

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The immune system targets virus-infected cells by different means. One of the essential antiviral mechanisms is apoptosis induced by ligation of tumor necrosis factor receptor 1 (TNFR1). This receptor can be activated by tumor necrosis factor alpha (TNF-␣), which upon binding to TNFR1 induces the assembly of first an inflammatory and later a proapoptotic signaling complex. Here, we report that infection by human herpesvirus 6B (HHV-6B) inhibited poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 and 8 activation, and IB␣ Ser-32 phosphorylation downstream of TNFR1, indicating inhibition of both the inflammatory and apoptotic signaling pathways. We identified a hitherto uncharacterized viral protein, U20, as sufficient for mediating this inhibition. U20 was shown to locate to the cell membrane, and overexpression inhibited PARP cleavage, caspase 3 and 8 activation, IB␣ Ser-32 phosphorylation, and NF-B transcriptional activity. Moreover, small interfering RNA (siRNA) knockdown of U20 demonstrated that the protein is necessary for HHV-6B-mediated inhibition of TNFR signaling during infection. These results suggest an important novel function of U20 as a viral immune evasion protein during HHV-6B infection.

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Detection of human herpesvirus‐6 in cerebrospinal fluid of patients with encephalitis

Cited by 94 publications

References 44 publications

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

U20 Is Responsible for Human Herpesvirus 6B Inhibition of Tumor Necrosis Factor Receptor-Dependent Signaling and Apoptosis

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