Evidence for Viral Etiology of Multiple Sclerosis

Tselis, Alexandros

doi:10.1055/s-0031-1287656

Cited by 69 publications

(66 citation statements)

References 60 publications

(66 reference statements)

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“…These viruses have been associated with significant adverse clinical outcomes in clinical situations in which substantial numbers of cells may be undergoing apoptosis, such as treatment with cytotoxic cancer chemotherapeutic agents, solid organ and bone marrow transplantation (18,19), and severe hypersensitivity and autoimmune disorders (20)(21)(22)(23)(24), and in patients critically ill from a variety of causes (25). Human herpesviruses have been implicated in a variety of incompletely understood clinical disorders (26), some of which may be associated with apoptosis. EBV is also known to cause lymphomas and nasopharyngeal carcinoma (reviewed in references 27 and 28).…”

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confidence: 99%

Activation of Human Herpesvirus Replication by Apoptosis

Prasad

Remick

Zeichner

2013

J Virol

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A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

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confidence: 99%

Activation of Human Herpesvirus Replication by Apoptosis

Prasad

Remick

Zeichner

2013

J Virol

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“…In comparison to the microbiome, the so-called virome [a collection of viruses within an individual, including viruses causing acute infection, such as influenza virus, as well as those associated with persistent or latent infection, such as cytomegalovirus (CMV)] and its impact on human health are relatively understudied and are in the early phases of characterization (1 ). One example of an area of great excitement is large, unbiased surveys that attempt to define a viral etiology for diseases that have been postulated to be attributed to a virus but for which no specific virus has been implicated, such as multiple sclerosis, certain malignancies, or Kawasaki disease (2,3 ).…”

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confidence: 99%

Your Viral Past: A Comprehensive Method for Serological Profiling to Explore the Human Virome

McAdam

2016

Clinical Chemistry

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“…It seems likely that the role of such pathogens is to enhance susceptibility to MS rather than directly induce disease. One of the strongest links in MS is viral infection [10], and a number of different viruses have been implicated including Epstein-Barr, human herpes virus 6, and human endogenous retroviruses [10][11][12]. Precisely how the viral infection contributes to MS development has not been clarified, but it may reflect the initial stimulation of immune cells to viral antigens or the induction of oligodendrocyte death as a result of viral infection.…”

Section: Introductionmentioning

confidence: 99%

Model Systems to Define Remyelination Therapies

Miller¹,

Karl²,

Tognatta³

et al. 2018

Neuroplasticity - Insights of Neural Reorganization

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Demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS), are characterized by multiple focal demyelinating lesions, resulting in various functional deficits. The pathology of MS is defined by local loss of myelin sheaths in the brain and spinal cord associated with infiltration of peripheral immune cells. Classically, MS starts with a series of relapses and remissions, followed several years later by a more progressive form of the disease and a steady functional decline. Although the mechanism of disease initiation is poorly understood, disease progression is associated with immune system activation toward CNS antigens including myelin proteins. Animal models of MS have been critical in the development of MS therapies, with experimental allergic encephalitis (EAE) being the most common. This model has been instrumental in defining the role of T cells in disease progression and in the development of targeted therapies. Understanding the biology of myelin repair has, however, largely come from other model systems including local targeted demyelination in vivo, slice preparations, and in vitro. This has led to the identification of a diverse array of potential new targets to modulate disease progression. Development of these new avenues is the target of intensive ongoing research.

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Evidence for Viral Etiology of Multiple Sclerosis

Cited by 69 publications

References 60 publications

Activation of Human Herpesvirus Replication by Apoptosis

Activation of Human Herpesvirus Replication by Apoptosis

Your Viral Past: A Comprehensive Method for Serological Profiling to Explore the Human Virome

Model Systems to Define Remyelination Therapies

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