Neuropsychiatric Sequelae of Nipah Virus Encephalitis

Ng, Beng-Yeong; Lim, C. C. Tchoyoson; Yeoh, Alice; Lee, W.L.

doi:10.1176/jnp.16.4.500

Cited by 50 publications

(23 citation statements)

References 14 publications

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“…One of the survivors, rNiV M -C ko W ko -4, developed a stark behavioral change, shifting from a very calm and docile demeanor to extremely aggressive behavior. Similar persistent behavioral disturbances, including increased irritability and violent outbursts, have been reported frequently for human survivors of NiV encephalitis (5,50).…”

Section: Discussionsupporting

confidence: 70%

“…Over time, the neurological signs diminished somewhat, and there were periods when no motor signs could be observed, but these would return a day or two later; this occurred multiple times in an undulating pattern. Although this study ended 35 days p.i., these sequelae are similar to the persistent gait disorders described for human survivors (1,5,50). The two surviving ferrets also exhibited dilated pupils and apparent visual deficits, possibly caused by oculomotor nerve palsy (cranial nerve III), which has been described as one of the neurological sequelae of some human survivors of NiV encephalitis (5).…”

Section: Discussionsupporting

confidence: 68%

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Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

Satterfield

Cross

Fenton

et al. 2016

J Virol

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Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. IMPORTANCE Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteinsin pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 68%

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

Satterfield

Cross

Fenton

et al. 2016

J Virol

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“…The neurological signs can include confusion, motor deficits, seizures, febrile encephalitic syndrome and a reduced level of consciousness. Even neuropsychiatric sequelae have been reported but it remains unclear whether a post-infectious encephalo-myelitis occurs following infection [141][142][143]. The use of animal models showed that the main route of entry into the CNS is the olfactory nerve [144] and that the Nipah virus may persist in different regions of the brain of grivets/green monkeys [145], reminiscent of relapsing and late-onset encephalitis observed in humans [146].…”

Section: Respiratory Viruses With Neuroinvasive and Neurotropic Propementioning

confidence: 99%

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

Desforges

Coupanec

Dubeau

et al. 2019

Viruses

941

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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“…The development of abnormal cognitive dysfunctions or mental retardation may be directly related to the acute encephalitis and some of the patients progress thereafter toward cerebellar atrophy and brainstem lesions. In addition, affection of the brain tissue might alter the transmission of the signal in the cortical and subcortical area of the brain in those patients and thus provoke serious neurological complications [49,50].…”

Section: Pathology In Humansmentioning

confidence: 99%

Henipavirus pathogenesis and antiviral approaches

Mathieu

Horvat

2015

Expert Review of Anti-infective Therapy

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Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field.

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Neuropsychiatric Sequelae of Nipah Virus Encephalitis

Cited by 50 publications

References 14 publications

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

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

Henipavirus pathogenesis and antiviral approaches

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