HHV‐6 and EBV DNA quantitation in lymph nodes of 86 patients with Hodgkin's lymphoma

Lacroix, Aurélie; Jaccard, Arnaud; Rouzioux, Christine; Piguet, Christophe; Petit, Barbara; Bron, Dominique; Ranger-Rogez, Sylvie

doi:10.1002/jmv.20868

Cited by 30 publications

(34 citation statements)

References 31 publications

(27 reference statements)

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“…This particularly concerns the nodular sclerosis form of the disease in young adults (143,197). Note that recent results found no association between ciHHV-6 and classical Hodgkin's disease (198).…”

Section: Chronic Infectionsmentioning

confidence: 95%

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: Chronic Infectionsmentioning

confidence: 95%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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“…In addition, evidence exists for an association between HHV-6B and mesial temporal lobe epilepsy (10,11). A number of studies have associated HHV-6A or -6B with different T-and B-cell lymphomas (20,21), although evidence for a direct role of the viruses is complicated by their ubiquitous nature and ability to integrate chromosomally (14). Possibly, HHV-6A or -6B might act as a cofactor in certain oncogenic diseases by promoting replication of other viruses, thereby helping the double-infected cells to evade the immune system (8).…”

mentioning

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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“…Le rôle du HHV-6 comme co-facteur du virus du VIH dans l'évolution vers le sida n'a jamais été formellement démontré chez les malades même si sa fréquence de détection est particulièrement élevée sur ce terrain [37]. En ce qui concerne la relation de causalité entre le HHV-6 et les tumeurs du tissu lymphoïde, le génome viral a été trouvé dans le tissu tumoral de malades atteints de lymphomes et de la maladie de Hodgkin, exceptionnellement sous une forme inté-grée au génome cellulaire [38,39]. Cependant, l'étude de sujets témoins indemnes de ces maladies montre que le HHV-6 est aussi fréquemment détectable dans le tissu lymphoïde, indépendamment de l'existence d'une tumeur [40].…”

Section: Réactivations Et Réinfections Exogènesunclassified