Association of human herpesvirus 6 and human herpesvirus 7 with demyelinating diseases of the nervous system

Tomsone, V; Logina, Ināra; Millers, Andrejs; Chapenko, Svetlana; Kozireva, Svetlana; Murovska, Modra

doi:10.1080/135502801753248150

Cited by 33 publications

(11 citation statements)

References 35 publications

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“…The central nervous system (CNS) seems to be one of the reservoirs for persistent HHV-7 infection, since specific genomic sequences can be detected by PCR ( 61 , 62 ). Nonetheless, HHV-7 reactivation measured by specific qPCR of blood samples is also associated with demyelinating diseases of the peripheral nervous system (PNS) ( 6 ). Most interestingly, we observed MneHV7-specific staining of nerve ganglia innervating the salivary glands.…”

Section: Discussionmentioning

confidence: 99%

“…Some of the cells stained in the nerve ganglia show a structure reminiscent of that of Schwann cells. Since HHV-7 reactivation is associated with demyelinating processes in humans ( 6 ), it is tempting to speculate that Schwann cells are susceptible to MneHV7 infection. MneHV7 lytic infection of Schwann cells could be associated with a decrease in myelin expression, resulting in demyelinating neuropathies.…”

Section: Discussionmentioning

confidence: 99%

“…While primary HHV-7 infection can result in benign illness, like exanthem subitum ( 3 ), viral reactivation in immunosuppressed patients has been associated with severe pathological conditions ( 4 , 5 ). Complications associated with virus reactivation include a wide range of diseases, including neurological pathologies ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

Staheli

Dyen

Deutsch

et al. 2016

J Virol

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Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases.IMPORTANCE Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

Staheli

Dyen

Deutsch

et al. 2016

J Virol

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“…Thus, in the last decades, it has been hypothesized that an environmental factor may be involved in the disease, triggering autoimmune attack against nerve cells in genetically susceptible individuals [5]. Recently, several articles [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25]have reported that human herpesvirus-6 (HHV-6), a highly prevalent virus in human population, could be this agent; two variants of HHV-6 (HHV-6A and HHV-6B) have been identified, but only the HHV-6A variant, a neurotropic virus, has been suggested to have a pathogenic role in MS, and specifically, in exacerbations [8, 17, 22]. …”

Section: Introductionmentioning

confidence: 99%

Beta-Interferon Treatment Reduces Human Herpesvirus-6 Viral Load in Multiple Sclerosis Relapses but Not in Remission

Álvarez‐Lafuente

Heras²,

Bartolomé³

et al. 2004

Eur Neurol

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To determine whether the DNA prevalence of human herpesvirus-6 (HHV-6), the viral load and the prevalence of both HHV-6 variants in relapsing-remitting multiple sclerosis (RRMS) patients in exacerbation are altered by beta-interferon (IFN-β) treatment, in comparison with RRMS patients in remission, we analyzed HHV-6 (A and B) genomes in 189 serum samples by quantitative real-time polymerase chain reaction: 105 of the RRMS patients were receiving IFN-β treatment (48 in exacerbation) and 84 were untreated (36 in relapse). The results were as follows. (1) Prevalence decrease because of IFN-β treatment was not significant: 25% of RRMS patients in relapse vs. 15.9% in remission (p = 0.45). (2) Viral load was twice as much in untreated patients in relapse than in treated ones. (3) We only found variant A. Since IFN-β treatment is able to significantly reduce HHV-6 viral load in RRMS patients in relapse, but not in remission, we suggest a role for HHV-6 in the pathogenesis of multiple sclerosis exacerbations and an antiviral role for IFN-β treatment in RRMS.

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“…It is not clear which factors are responsible for the different courses [9]. No virus has been definitively implicated as a causative factor of MS, but certain HHVs have been linked with the development of MS [10, 11]. Since the first papers linking HHV-6 to MS appeared in 1993 [12] many others have presented contradictory results on its possible role in the disease.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of Active Human Herpes Virus 6 Infection in Iranian Patients with Different Subtypes of Multiple Sclerosis

Ramroodi

Sanadgol

Ganjali

et al. 2013

Journal of Pathogens

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Background. Recently, it has been suggested that human herpes virus 6 (HHV6) may play a role in the pathogenesis of multiple sclerosis (MS). Our purpose is to determine the incidence of reactivated HHV6 in MS patients. Methods. Viral sequence analyzed by qPCR in the peripheral blood mononuclear cells (PBMCs), serum, and saliva samples of different subtypes of MS patients (n = 78) and healthy controls (n = 123). HHV6 IgG and IgM antibody levels measured by ELISA technique in the plasma samples of both groups. Likewise, cerebrospinal fluid (CSF) samples of some MS patients (n = 38) were analyzed for viral sequence. Results. Results demonstrate increased levels of anti-HHV6-IgG (78.2% versus 76.4% in controls; P = NS), and IgM (34.6% versus 6.5% in controls; P < 0.05) in MS patients. Furthermore, RRMS and SPMS patients showed relatively higher anti-HHV6 IgG and IgM compared to PPMS (P < 0.001). Moreover, load of cell-free viral DNA was higher in RRMS and SPMS patients and detected in 60.2% (47/78) of MS patients, compared with 14.6% (18/123) of healthy controls (P < 0.001). Moreover, load of cell-free viral DNA was higher in RRMS and SPMS patients and detected in 60.2% (47/78) of MS patients, compared with 14.6% (18/123) of healthy controls (P < 0.001). Conclusions. The results extend the observation of an increased frequency of systemic reactivated HHV6 infection in MS patients with developed stages of disease.

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Association of human herpesvirus 6 and human herpesvirus 7 with demyelinating diseases of the nervous system

Cited by 33 publications

References 35 publications

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

Beta-Interferon Treatment Reduces Human Herpesvirus-6 Viral Load in Multiple Sclerosis Relapses but Not in Remission

Monitoring of Active Human Herpes Virus 6 Infection in Iranian Patients with Different Subtypes of Multiple Sclerosis

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