Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children

Merelli, E.; Bedin, Roberta; Sola, Patrizia; Barozzi, Patrizia; Mancardi, Gianluigi; Ficarra, Guido; Franchini, Genoveffa

doi:10.1007/s004150050121

Cited by 93 publications

(60 citation statements)

References 24 publications

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“…Among them, HHV-6 appears to be one of the most serious candidates in the category of infectious triggers, on the basis of immunological, virological, and experimental data (6). These data include the isolation of this virus from diseased CNS tissues of MS patients, serologic studies of HHV-6 antibody reactivity in their sera and CSF, and in situ detection of HHV-6 DNA transcripts (141,183,(185)(186)(187)(188). This hypothesis also results from general considerations founded on the neurotropism of the virus combined with its theoretical capacity to induce both neuroinflammation and autoimmunity.…”

Section: Chronic Infectionsmentioning

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: Chronic Infectionsmentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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“…More recent studies demonstrated higher titers of antibodies to HHV-6 and cell-free DNA of HHV-6 in serum and cerebrospinal fluid (CSF) of MS patients, suggesting reactivation of HHV-6 in MS (1-2, 4, 20-23, 29, 35-37, 46, 50). However, other investigators found no differences in these measurements between MS patients and control subjects, failing to confirm such an association (6,14,24,26,28,30,41). It is important to note that the assays reported in some of these studies were based on the whole HHV-6 virus, which contains viral protein components sharing extensive amino-acid-sequence homology with other related viral proteins, such as CMV and HHV-7, thus making the results difficult to interpret.…”

mentioning

confidence: 93%

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Tejada‐Simon

Zang

Hong

et al. 2002

J Virol

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Human herpesvirus 6 (HHV-6), a latent lymphotropic and neurotropic virus, has been suspected as an etiologic agent in multiple sclerosis (MS). The study was undertaken to correlate virologic evidence for HHV-6 activity with the state of host immunity to HHV-6 in MS patients and control subjects. The study revealed that cell-free DNA of HHV-6 was detected more frequently in both serum and cerebrospinal fluid of MS patients than in those of control subjects. T cells recognizing the recombinant 101-kDa protein (101K) corresponding to the major immunoreactive region unique to HHV-6 occurred at significantly lower precursor frequency in MS patients than in control subjects. The resulting HHV-6-specific T-cell lines obtained from MS patients exhibited skewed cytokine profiles characterized by the inability to produce interleukin-4 (IL-4) and IL-10. The decreased T-cell responses to HHV-6 and the altered cytokine profile were consistent with significantly declined serum immunoglobulin G (IgG) titers for HHV-6 of MS patients compared to those of control subjects. In contrast, elevated serum IgM titers for HHV-6 were detected in the majority of MS patients, which may reflect frequent exposure of B cells to HHV-6. The findings suggest that the decreased immune responses to HHV-6 may be responsible for ineffective clearance of HHV-6 in MS patients.

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“…However, other reports have failed to detect serologic (Nielsen et al, 1997) or virologic (Sanders et al, 1996;Martin et al, 1997;Merelli et al, 1997) evidence of an association between HHV-6 and MS. As such, de®nitive proof of a role for HHV-6 in the pathogenesis of MS awaits further study.…”

Section: Multiple Sclerosismentioning

confidence: 92%

Human Herpesvirus-6: Neurologic Implications of a Newly-Described Viral Pathogen

Kimberlin

Whitley

1998

J Neurovirol

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Discovered only 12 years ago, human herpesvirus-6 (HHV-6) has been associated with central nervous system (CNS) ®ndings such as febrile seizures, encephalitis, meningitis, and possibly multiple sclerosis. These manifestations have been reported in both immunocompetent and immunocompromised individuals. The applications of such sophisticated laboratory tools as polymerase chain reaction, in situ hybridization, immunohistochemical staining, and representational difference analysis have expanded knowledge of the spectrum of CNS disease attributable to HHV-6 while delineating pathogenic mechanisms of both primary HHV-6 infection and reactivation from latency. This article reviews existing knowledge of the CNS manifestations of HHV-6, focusing on both clinical aspects of HHV-6 infection and its pathogenesis on neurologic diseases.

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Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children

Cited by 93 publications

References 24 publications

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Human Herpesvirus-6: Neurologic Implications of a Newly-Described Viral Pathogen

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