Diagnostic assays for active infection with human herpesvirus 6 (HHV-6)

Caserta, Mary T.; Hall, Caroline Breese; Schnabel, Kenneth C.; Lofthus, Geraldine; Mariño, Andrea; Shelley, Lynne; Yoo, Christina; Carnahan, Jennifer; Anderson, Linda; Wang, Hongyue

doi:10.1016/j.jcv.2010.02.007

Cited by 78 publications

(55 citation statements)

References 14 publications

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“…By means of numerous assays based on real-time PCR, HHV-6 DNA can be detected and reproducibly quantified in a broad range of clinical specimens, including whole blood, cerebrospinal fluid, and any other bodily fluid or tissue (110,119,120). The methods are financially accessible, quick, safe, and currently widespread.…”

Section: Direct Diagnosismentioning

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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Section: Direct Diagnosismentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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“…Second, one needs to be able to transmit infection from CIHHV-6-carrying cells to uninfected cells, and third, to demonstrate that the newly infecting virus matches the one integrated. Attempts by several groups have failed at demonstrating HHV-6 reactivation from CIHHV-6-infected cells (7,14,21,24). However, in a recent paper, Arbuckle et al suggest that reactivation does occur, since treating T cells from individuals carrying CIHHV-6 with the histone deacetylase inhibitor trichostatin A results in a 1.5-to 2-fold increase in the copy numbers of HHV-6A (6).…”

Section: Chromosomal Integration Of Hhv-6mentioning

confidence: 99%

“…The inability of practitioners to distinguish bona fide viral loads originating from active viral reactivation from high DNA loads due to CIHHV-6 is probably the first established consequence of viral integration. CIHHV-6 patients have high DNA loads (and not high viral loads) that are unaffected by antiviral medications (14,42). This misdiagnosis results in patients receiving unnecessary treatments, and antiviral therapies can have potentially serious consequences for some patients (e.g., bone marrow transplant recipients).…”

Section: Consequences Of Cihhv-6 For Diagnosismentioning

confidence: 99%

Herpesviruses and Chromosomal Integration

Morissette

Flamand

2010

J Virol

199

159

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Herpesviruses are members of a diverse family of viruses that colonize all vertebrates from fish to mammals. Although more than one hundred herpesviruses exist, all are nearly identical architecturally, with a genome consisting of a linear double-stranded DNA molecule (100 to 225 kbp) protected by an icosahedral capsid made up of 162 hollow-centered capsomeres, a tegument surrounding the nucleocapsid, and a viral envelope derived from host membranes. Upon infection, the linear viral DNA is delivered to the nucleus, where it circularizes to form the viral episome. Depending on several factors, the viral cycle can proceed either to a productive infection or to a state of latency. In either case, the viral genetic information is maintained as extrachromosomal circular DNA. Interestingly, however, certain oncogenic herpesviruses such as Marek's disease virus and Epstein-Barr virus can be found integrated at low frequencies in the host's chromosomes. These findings have mostly been viewed as anecdotal and considered exceptions rather than properties of herpesviruses. In recent years, the consistent and rather frequent detection (in approximately 1% of the human population) of human herpesvirus 6 (HHV-6) viral DNA integrated into human chromosomes has spurred renewed interest in our understanding of how these viruses infect, replicate, and propagate themselves. In this review, we provide a historical perspective on chromosomal integration by herpesviruses and present the current state of knowledge on integration by HHV-6 with the possible clinical implications associated with viral integration.

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“…В образцах плазмы пациентов с реактивацией инфек-ции концентрация обычно составляет более 10 3 ко-пий/мл [56]. ПЦР с использованием обратной транс-криптазы позволяет дифференцировать латентную инфекцию и ее реактивацию [53,57].…”

Section: российский вестник перинатологии и педиатрии 2016; 61:5 Rosunclassified

Infections caused by herpes virus type 6: modern features

Анохин¹,

Sabitova²

2016

Ross. vestn. perinatol. pediatr.

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Diagnostic assays for active infection with human herpesvirus 6 (HHV-6)

Cited by 78 publications

References 14 publications

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Herpesviruses and Chromosomal Integration

Infections caused by herpes virus type 6: modern features

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