Detection of Antibodies Directed against Human Herpesvirus 6 U94/REP in Sera of Patients Affected by Multiple Sclerosis

Caselli, Elisabetta; Boni, Michela; Bracci, Arianna; Rotola, Antonella; Cermelli, Claudio; Castellazzi, Massimiliano; Luca, Dario Di; Cassai, Enzo

doi:10.1128/jcm.40.11.4131-4137.2002

Cited by 41 publications

(39 citation statements)

References 50 publications

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“…The same is true for reports on an altered humoral or tissue-specific immune response in MS patients (expressed as serum IgM or CSF IgG levels or lymphoproliferative responses towards HHV-6 antigens) (63,74,119,368,370,397). In one study, higher prevalence and higher antibody titers towards HHV-6 pU94 were found and it was concluded that MS patients may undergo a different exposure to HHV-6 than controls (56). Several authors who found HHV-6A more prevalent than HHV-6B have pointed at the importance of subtyping HHV-6-positive cases (7,13,208,370).…”

Section: Clinical Manifestations Of Hhv-6 Infectionmentioning

confidence: 79%

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

2005

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Human herpesvirus 6 (HHV-6) is a betaherpesvirus that is closely related to human cytomegalovirus. It was discovered in 1986, and HHV-6 literature has expanded considerably in the past 10 years. We here present an up-to-date and complete overview of the recent developments concerning HHV-6 biological features, clinical associations, and therapeutic approaches. HHV-6 gene expression regulation and gene products have been systematically characterized, and the multiple interactions between HHV-6 and the host immune system have been explored. Moreover, the discovery of the cellular receptor for HHV-6, CD46, has shed a new light on HHV-6 cell tropism. Furthermore, the in vitro interactions between HHV-6 and other viruses, particularly human immunodeficiency virus, and their relevance for the in vivo situation are discussed, as well as the transactivating capacities of several HHV-6 proteins. The insight into the clinical spectrum of HHV-6 is still evolving and, apart from being recognized as a major pathogen in transplant recipients (as exemplified by the rising number of prospective clinical studies), its role in central nervous system disease has become increasingly apparent. Finally, we present an overview of therapeutic options for HHV-6 therapy (including modes of action and resistance mechanisms)

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Section: Clinical Manifestations Of Hhv-6 Infectionmentioning

confidence: 79%

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

2005

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“…In several retrospective studies, MS patients have significantly higher EBV IgG titres than healthy controls (Table 3), which is also the case in studies on HHV-6 [28,[47][48][49] and endogenous retrovirus [50]. This has been interpreted as an involvement of these viruses in MS, but it is important to notice that MS patients have also increased IgG titres against other viruses, such as measles virus, which is not involved in the disease [6].…”

Section: Detection Of Antibodies In Bloodmentioning

confidence: 91%

Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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The aetiology and pathogenesis of MS are unknown, but environmental agents, genetic susceptibility and stochastic events are likely to be involved. In order to evaluate the possibility that MS is linked to EBV infection, we here evaluate studies on MS- and EBV-epidemiology, prospective and retrospective analysis of EBV-serology, investigations of EBV DNA sequences in blood and tissues, specificity of antibodies in oligoclonal bands in MS patients and results from antiviral chemotherapy of MS patients. It could be demonstrated that EBV is complying with the epidemiological observations in MS and that all MS patients are seropositive to EBV in contrast to healthy controls. Importantly, despite difficulties in diagnosing child-MS, the vast majority of these patients are also EBV seropositive. In contrast to control groups, recent EBV infections have never been observed in children or adults with MS. Further prospective studies indicate a 2.8 times higher tendency for development of MS after infectious mononucleosis. In MS patients, unbiased analyses pull out EBV antigens as high-affinity targets for the antibodies in the oligoclonal bands. Humans are the exclusive natural host for EBV, a finding that may explain why MS is unique to humans. Together these unique observations strongly suggest a linkage between MS and EBV infection. Infection by EBV offers numerable mechanisms to perturb the immune system, including mimicry and superantigen induction, which may potentially participate in the disease mechanisms. In contrast, studies demonstrating higher IgG titres and occurrence of viral DNA in serum/plasma are likely to reflect a consequence of the disease. An explanation for a potential role of respiratory diseases in MS is discussed. It is concluded that the ultimate test to the hypothesis of MS and EBV is the development and application of an EBV vaccine, which is predicted to eradicate the disease.

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“…As indicated previously, the presence and amount of U94 transcripts might reflect episomal latency and, in some cases, ciHHV-6. Moreover, a recombinant U94 protein has been used to create an ELISA that would be suitable for exploring the antiviral immune response in HHV-6-related chronic diseases (141). However, the relevance of U94-related markers remains to be demonstrated formally.…”

Section: Latent Infectionmentioning

confidence: 99%

“…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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Detection of Antibodies Directed against Human Herpesvirus 6 U94/REP in Sera of Patients Affected by Multiple Sclerosis

Cited by 41 publications

References 50 publications

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

Multiple sclerosis is linked to Epstein‐Barr virus infection

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

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