Abstract

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.

Highlights

  • The central nervous system (CNS), a marvel of intricate cellular and molecular interactions, maintains life and orchestrates homeostasis

  • These peculiar events usually take place when RNA viruses like influenza A, human coronaviruses, such as Middle-East Respiratory Syndrome (MERS)-CoV and Severe Acute Respiratory Syndrome (SARS)-CoV, or henipaviruses, present in an animal reservoir, cross the species barrier as an opportunistic strategy to adapt to new environments and/or new hosts

  • Has recently been shown to exacerbate experimental autoimmune encephalomyelitis (EAE), which is reminiscent of the observation that multiple sclerosis (MS) relapses have been associated with viral infections of the upper respiratory tract [163,164,165]

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Summary

Introduction

The central nervous system (CNS), a marvel of intricate cellular and molecular interactions, maintains life and orchestrates homeostasis. In addition to the many “regular” viruses that circulate and infect millions of people every year, new respiratory viral agents emerge from time to time, causing viral epidemics or pandemics associated with more serious symptoms [21,22], such as neurologic disorders. These peculiar events usually take place when RNA viruses like influenza A, human coronaviruses, such as MERS-CoV and SARS-CoV, or henipaviruses, present in an animal reservoir, cross the species barrier as an opportunistic strategy to adapt to new environments and/or new hosts. These zoonoses may have disastrous consequences in humans [23,24,25,26,27,28,29], and the burden is even higher if they have neurological consequences

Viruses as Plausible Etiologic Agents in Neurological Disorders
Respiratory Viruses with Neuroinvasive and Neurotropic Properties
Human Coronaviruses
Possible Mechanisms of HCoV Neuroinvasiveness
Human Coronaviruses in the CNS
Mechanisms of HCoV-Induced Neurodegeneration
Conclusions
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