Review, part 1: Human herpesvirus‐6‐basic biology, diagnostic testing, and antiviral efficacy

Flamand, Louis; Komaroff, Anthony L.; Arbuckle, Jesse H.; Medveczky, Peter G.; Ablashi, Dharam V.

doi:10.1002/jmv.21839

Cited by 61 publications

(57 citation statements)

References 85 publications

(105 reference statements)

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“…Taken as a whole, the differences between HHV-6A and HHV-6B are believed to induce noticeable dissimilarities in the virus replication cycle, in particular regarding splicing patterns and the temporal regulation of gene transcription. Those differences may also affect the binding of viral proteins to their cellular targets, which in turn may alter cell tropism, interactions with the microenvironment, host immune responses, and, ultimately, pathogenesis (4,22). Note that no recombinant virus originating from a mixed infection with HHV-6A and HHV-6B has ever been identified, although recent results provide some evidence of recombination between ciHHV-6A and ciHHV-6B (32).…”

Section: Genome and Genetic Variabilitymentioning

confidence: 99%

“…In addition, independently of any complete virus-producing process, the expression of certain HHV-6 genes might occur from persisting episomal or ciHHV-6 forms of viral DNA. Many publications have reviewed the formally demonstrated or putative effects of virally encoded gene products on the regulation and modification of cell functions (3,4,8). As an example, considering the gene products of the IE-A region, IE2 might behave as a general transcriptional activator of many viral and cellular genes, while IE1 interacts with PML bodies (71,72).…”

Section: Impacts Of Viral Gene Expression On Cell Functionsmentioning

confidence: 99%

“…Like other herpesviruses, HHV-6 exhibits a wide range of biological properties which might explain its ability to both stimulate and modulate immune responses (3,4,8). This modulation, in turn, would permit evasion of the HHV-6-specific immune response and improve the microenvironmental conditions for promoting virus persistence.…”

Section: Interactions With the Immune Systemmentioning

confidence: 99%

“…Valomaciclovir, a drug developed initially against varicella-zoster virus, has also shown significant activity against HHV-6 in vitro (214)(215)(216). Other antiviral compounds have demonstrated promising experimental anti-HHV-6 activity, including the nucleoside/nucleotide analogues SS2242, A-5021, cyclopropavir, and 3-deaza-HPMPA and the nonnucleoside inhibitor CMV423 (4,(217)(218)(219)(220)(221)(222). These are all still at a step of preclinical development.…”

Section: Antiviral Agentsmentioning

confidence: 99%

“…The importance of the finding was amplified by the fact that this virus, finally designated human herpesvirus 6 (HHV-6), was initially isolated from patients with lymphoproliferative disorders and AIDS, raising the key question of its pathogenicity. Since that time, the knowledge about this virus and associated diseases has considerably improved, as extensively reported in previously published overviews and books which remain relevant references (2)(3)(4)(5)(6)(7)(8)(9)(10). However, many questions on those domains are still pending and constitute true challenges for present and future research.…”

mentioning

confidence: 99%

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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: Genome and Genetic Variabilitymentioning

confidence: 99%

Section: Impacts Of Viral Gene Expression On Cell Functionsmentioning

confidence: 99%

Section: Interactions With the Immune Systemmentioning

confidence: 99%

Section: Antiviral Agentsmentioning

confidence: 99%

mentioning

confidence: 99%

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Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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Viral Infections

Sterling

2016

Rook's Textbook of Dermatology, Ninth Edition

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Viral Infections

Harwood,

Sterling

2024

Rook's Textbook of Dermatology

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Viruses can cause disease in the skin or mucosa by direct infection or, via a systemic infection, produce secondary skin abnormalities. The chapter reviews the viruses associated with skin lesions, outlining the pathophysiology, the clinical features, diagnostic methods and the approaches to treatment. Primary skin infection following direct contact occurs with poxviruses, some herpesviruses and papillomaviruses leading to visible features which may be readily diagnostic. Less specific skin changes are seen with systemic infections, when infection is often via mucosae or inoculation, for example with parvovirus, measles or coronavirus and for these infections, diagnosis will usually involve body fluid analysis.

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Review, part 1: Human herpesvirus‐6‐basic biology, diagnostic testing, and antiviral efficacy

Cited by 61 publications

References 85 publications

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Viral Infections

Viral Infections

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