Blue Moon Neurovirology: The Merits of Studying Rare CNS Diseases of Viral Origin

O’Donnell, Lauren A.; Rall, Glenn F.

doi:10.1007/s11481-010-9200-4

Cited by 17 publications

(18 citation statements)

References 105 publications

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“…Nonrestricted virus replication results in cytolytic viral replication in brain tissue (6,58,59). There are no specific therapies for these complications of CNS infection (23,51,60,61), and attempts to treat SSPE with various antiviral drugs, including ribavirin, interferons, and isoprinosin, have been disappointing (2,4,21,23,51,(60)(61)(62). Here, we provide evidence that MV HRC-derived peptides have the potential to fill this void.…”

Section: Discussionmentioning

confidence: 84%

Fatal Measles Virus Infection Prevented by Brain-Penetrant Fusion Inhibitors

Welsch

Talekar

Mathieu

et al. 2013

J Virol

106

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e Measles virus (MV) infection causes an acute childhood disease that can include infection of the central nervous system and can rarely progress to severe neurological disease for which there is no specific treatment. We generated potent antiviral peptide inhibitors of MV entry and spreading and MV-induced cell fusion. Dimers of MV-specific peptides derived from the C-terminal heptad repeat region of the MV fusion protein, conjugated to cholesterol, efficiently protect SLAM transgenic mice from fatal MV infection. Fusion inhibitors hold promise for the prophylaxis of MV infection in unvaccinated and immunocompromised people, as well as potential for the treatment of grave neurological complications of measles.

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Section: Discussionmentioning

confidence: 84%

Fatal Measles Virus Infection Prevented by Brain-Penetrant Fusion Inhibitors

Welsch

Talekar

Mathieu

et al. 2013

J Virol

106

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“…CNS complications of MV infection may occur soon after infection in the case of acute encephalomyelitis, or years after infection, as a result of viral persistence in subacute sclerosing panencephalitis (SSPE) and progressive infectious encephalitis or measles inclusion body encephalitis (MIBE). There are no specific therapies for acute complications of MV or for persistent MV infections (85)(86)(87)(88). Since we expect our proposed antiviral strategy to be host factor independent, it will fill a specific need for immunocompromised people at risk for MV infection, who cannot be vaccinated or do not respond adequately to vaccine.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Mathieu

Huey

Jurgens

et al. 2015

J Virol

100

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Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS)and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.

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“…Although rare, viral infections of the CNS do occur [2]. However, their incidence in clinical practice common virus, is associated with febrile illness, fever, cough and congestion [97,98], as well as a characteristic rash and Koplik's spots [99]. In rare circumstances, significant long-term CNS diseases, such as [99] post-infectious encephalomyelitis (PIE) or acute disseminated encephalomyelitis (ADEM), occur in children and adolescents.…”

Section: Introductionmentioning

confidence: 99%

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Desforges

Coupanec

Dubeau

et al. 2019

Viruses

931

997

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Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

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Blue Moon Neurovirology: The Merits of Studying Rare CNS Diseases of Viral Origin

Cited by 17 publications

References 105 publications

Fatal Measles Virus Infection Prevented by Brain-Penetrant Fusion Inhibitors

Fatal Measles Virus Infection Prevented by Brain-Penetrant Fusion Inhibitors

Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

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