Human Herpesvirus 6 and Neuroinflammation

Human herpesvirus (HHV-) 6A and HHV-6B are two distinct β-herpesviruses which have been associated with various neurological diseases, including encephalitis, meningitis, epilepsy, and multiple sclerosis. Although the reactivation of both viruses is recognized as the cause of some neurological complications in conditions of immunosuppression, their involvement in neuroinflammatory diseases in immunocompetent people is still unclear, and the mechanisms involved have not been completely elucidated. Here, we review the available data providing evidence for the capacity of HHV-6A and -6B to infect the central nervous system and to induce proinflammatory responses by infected cells. We discuss the potential role of both viruses in neuroinflammatory pathologies and the mechanisms which could explain virus-induced neuropathogenesis.

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The role of human herpesvirus-6 and inflammatory markers in the pathogenesis of multiple sclerosis

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2020.577313 ◽

2020 ◽

Vol 346 ◽

pp. 577313 ◽

Cited By ~ 1

Author(s):

Hossein Keyvani ◽

Hamid Zahednasab ◽

Hussain ali abraham Aljanabi ◽

Muhammad Asadi ◽

Rasoul Mirzaei ◽

...

Keyword(s):

Multiple Sclerosis ◽

Inflammatory Markers ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

Herpesvirus 6

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Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report

Multiple Sclerosis Journal ◽

10.1177/135245859800400606 ◽

1998 ◽

Vol 4 (6) ◽

pp. 490-496 ◽

Cited By ~ 67

Author(s):

D V Ablashi ◽

W Lapps ◽

M Kaplan ◽

J E Whitman ◽

J R Richert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mononuclear Cells ◽

Neurological Diseases ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

Igg Antibody ◽

Peripheral Blood Mononuclear ◽

Barr Virus ◽

Early Protein ◽

Herpesvirus 6

We examined cerebra! spinal fluid (CSF) from multiple sclerosis (MS) patients and patients with other neurological diseases (OND) for antibody specific for Human Herpesvirus-6 (HHV-6) and for HHV-6 DNA detectable by PCR. CSF from MS patients had a higher frequency of IgG antibody to HHV-6 late antigens (39.4%) compared with CSF from OND (7.4%). In contrast, the frequency of detectable IgG antibody in CSF from MS patients specific for Epstein-Barr Virus (EBV) (12.1%) and Human Cytomegalovirus (HCMV) (6.1%) was much lower. Two of 12 MS CSFs (16.7%) also contained HHV-6 DNA detected by PCR. None of four OND CSF were positive for HHV-6 DNA. Plasma from 16 patients with MS, eight with OND and 72 healthy donors were tested for antibodies by ELISA to HHV-6 early (p41/38) and late (gp 110) proteins. Although no differences in ant-gp 110 IgG antibody were detected between MS patients, patients with other neurological diseases, and normals, IgG antibody to early protein p41/38 was detected in > 68% of the plasma from MS patients, 12.5% from OND patient and 27.8% of the controls. IgM antibody to p41/38 was present in >56% of MS patients, 12.5% of OND patients, and 19% of controls. These data suggest that more than half of the MS patients had active, ongoing HHV-6 infections. HHV-6 was also isolated from peripheral blood mononuclear cells (PBMC) from 3/5 MS patients who were in relapse or had progressive disease and was identified as HHV-6 Variant B. These preliminary results support the hypothesis that HHV-6 may be a co-factor in the pathogenesis of some cases of MS.

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Insights into multiple sclerosis provided by non-coding RNAs: meeting summary from the symposium ‘Non-coding RNAs in autoimmune disorders of the central nervous system’ on 5 April 2013 in Warsaw, Poland

Multiple Sclerosis Journal ◽

10.1177/1352458514521518 ◽

2014 ◽

Vol 20 (11) ◽

pp. 1439-1442 ◽

Cited By ~ 1

Author(s):

Marcin P Mycko ◽

Howard L Weiner ◽

Krzysztof W Selmaj

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cell Biology ◽

Potential Role ◽

Mechanisms Of Action ◽

Ribonucleic Acids ◽

The Central Nervous System ◽

Non Coding Rnas ◽

Autoimmune Demyelination

More than 80% of the human genome is biochemically active, whereas less than 3% of the genome encodes proteins. The emerging field of non-coding ribonucleic acids (RNAs) that are products of the genome, but do not program proteins, has revolutionized our understanding of cell biology. This was followed by a growing interest in the role of non-coding RNAs in the pathogenesis of human diseases, including multiple sclerosis (MS). In April 2013, a symposium in Warsaw, Poland, was the first meeting entirely dedicated to advances in the understanding of the roles of various subclasses of non-coding RNAs and showcased their involvement in autoimmune demyelination and MS. New mechanisms of action of small non-coding RNAs, as well as the advent of long non-coding RNAs were discussed, including the potential role of non-coding RNAs as MS biomarkers and their use for therapeutic intervention in MS.

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73: Human herpesvirus 6 and multiple sclerosis: detection by quantitative real-time PCR and role of complement-mediated damage secondary to CD46 inactivation

Journal of Clinical Virology ◽

10.1016/s1386-6532(06)70092-0 ◽

2006 ◽

Vol 37 ◽

pp. S117 ◽

Cited By ~ 1

Author(s):

P. Lusso ◽

L. De Filippis ◽

C. Foglieni ◽

A.L. Vescovi ◽

G. Locatelli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Real Time ◽

Real Time Pcr ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

Quantitative Real Time Pcr ◽

Herpesvirus 6

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Multiple sclerosis and herpesvirus interaction

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130160 ◽

2013 ◽

Vol 71 (9B) ◽

pp. 727-730 ◽

Cited By ~ 11

Author(s):

Guilherme Sciascia do Olival ◽

Bruna Mendonca Lima ◽

Laura M. Sumita ◽

Vitor Serafim ◽

Maria Cristina Fink ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Demyelinating Disease ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

The Central Nervous System ◽

Herpesvirus 6 ◽

Epstein Barr

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

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The Potential Role of COVID-19 in the Pathogenesis of Multiple Sclerosis—A Preliminary Report

Viruses ◽

10.3390/v13102091 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2091

Author(s):

Noothan J. Satheesh ◽

Salam Salloum-Asfar ◽

Sara A. Abdulla

Keyword(s):

Multiple Sclerosis ◽

Preliminary Report ◽

Potential Role ◽

Acute Disseminated Encephalomyelitis ◽

Spanish Flu ◽

The Central Nervous System ◽

Glial Cell Interactions ◽

The Impact ◽

Hematogenous Route

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. However, it is understood that SARS-CoV-2 is neurotoxic and neuro-invasive and could enter the central nervous system (CNS) via the hematogenous route or via the peripheral nerve route and causes encephalitis, encephalopathy, and acute disseminated encephalomyelitis (ADEM) in COVID-19 patients. This review discusses the possibility of SARS-CoV-2-mediated Multiple Sclerosis (MS) development in the future, comparable to the surge in Parkinson’s disease cases following the Spanish Flu in 1918. Moreover, the SARS-CoV-2 infection is associated with a cytokine storm. This review highlights the impact of these modulated cytokines on glial cell interactions within the CNS and their role in potentially prompting MS development as a secondary disease by SARS-CoV-2. SARS-CoV-2 is neurotropic and could interfere with various functions of neurons leading to MS development. The influence of neuroinflammation, microglia phagocytotic capabilities, as well as hypoxia-mediated mitochondrial dysfunction and neurodegeneration, are mechanisms that may ultimately trigger MS development.

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Human herpesvirus 6 infects the central nervous system of multiple sclerosis patients in the early stages of the disease

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1045oa ◽

2004 ◽

Vol 10 (4) ◽

pp. 348-354 ◽

Cited By ~ 50

Author(s):

A Rotola ◽

I Merlotti ◽

L Caniatti ◽

E Caselli ◽

E Granieri ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Human Herpesvirus ◽

Clinical Samples ◽

Human Herpesvirus 6 ◽

Early Stages ◽

The Central Nervous System ◽

Herpesvirus 6 ◽

Multiple Sclerosis Patients

The presence and the replicative state of human herpesvirus 6 (HHV-6) were evaluated in clinical samples from multiple sclerosis (MS) patients at the first time of MS diagnosis. HHV-6 variant B was present in peripheral blood mononuclear cells of 5/32 (15%) patients, but persisted with a latent infection. Viral sequences were present also in cerebrospinal fluid (CSF), both free in the liquid (7/32, 22%) and latent in the cellular fraction (3/32, 9%), as shown by analysis of viral transcription. In these cases, variant A was detected. HHV-6 DNA sequences present in the CSF were associated to mature viral particles. In fact, in vitro infectious assays of CSF showed the presence of replication-competent virions. These results show that about 20% of MS patients have active foci of HHV-6 variant A infection in the early stages of the disease and suggest that viral replication takes place within the central nervous system.

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Is There a Role for Human Herpesvirus–6 in the Course of Multiple Sclerosis?

International Journal of MS Care ◽

10.7224/1537-2073-4.1.30 ◽

2002 ◽

Vol 4 (1) ◽

pp. 30-39 ◽

Cited By ~ 1

Author(s):

Silvia Delgado ◽

Micheline McCarthy

Keyword(s):

Multiple Sclerosis ◽

Viral Infection ◽

Human Herpesvirus ◽

Focused Attention ◽

Human Herpesvirus 6 ◽

Animal Virus ◽

The Past ◽

Specific Factors ◽

Herpesvirus 6

Historically multiple sclerosis (MS) has been associated with many different viruses, including several members of the Herpesviridae family. However, no human or animal virus has been identified as a true “cause” of MS; rather, the epidemiologic and diagnostic data suggest that viral infection may be a cofactor affecting the pathogenesis of MS. Human herpesvirus-6 (HHV-6) is a ubiquitous herpesvirus associated with a common childhood illness, roseola, and this virus is one of those most recently associated with MS. During the past decade, a number of investigations have examined anti—HHV-6-specific antibody responses, HHV-6 viral DNA, or HHV-6 presence in central nervous system (CNS) tissue in both MS patients and controls. There is a growing body of evidence associating HHV-6 infection of the CNS with MS in at least a subpopulation of patients, although the specific factors that define the vulnerable subpopulation(s) of MS patients have not been elucidated. This evidence is provocative but not definitive, and it does not distinguish between HHV-6 as a causal agent in MS versus HHV-6 as a cofactor. Although more clinically based data are needed, the controversy surrounding HHV-6 and MS has again focused attention on the role of viral infection in the clinical and pathologic course of MS. (Int J MS Care. 2002; 4: 30–31, 36–39)

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The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

Current Neuropharmacology ◽

10.2174/1570159x17666191113101629 ◽

2020 ◽

Vol 18 (5) ◽

pp. 408-430 ◽

Cited By ~ 5

Author(s):

Katarzyna Chamera ◽

Ewa Trojan ◽

Magdalena Szuster-Głuszczak ◽

Agnieszka Basta-Kaim

Keyword(s):

Potential Role ◽

Neurological Diseases ◽

Receptor Signalling ◽

Bidirectional Communication ◽

Key Factor ◽

Specific Localization ◽

The Central Nervous System ◽

Cell Type Specific ◽

Clusters Of Differentiation

: The bidirectional communication between neurons and microglia is fundamental for the proper functioning of the central nervous system (CNS). Chemokines and clusters of differentiation (CD) along with their receptors represent ligand-receptor signalling that is uniquely important for neuron – microglia communication. Among these molecules, CX3CL1 (fractalkine) and CD200 (OX-2 membrane glycoprotein) come to the fore because of their cell-type-specific localization. They are principally expressed by neurons when their receptors, CX3CR1 and CD200R, respectively, are predominantly present on the microglia, resulting in the specific axis which maintains the CNS homeostasis. Disruptions to this balance are suggested as contributors or even the basis for many neurological diseases. : In this review, we discuss the roles of CX3CL1, CD200 and their receptors in both physiological and pathological processes within the CNS. We want to underline the critical involvement of these molecules in controlling neuron – microglia communication, noting that dysfunctions in their interactions constitute a key factor in severe neurological diseases, such as schizophrenia, depression and neurodegeneration-based conditions.

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