Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans

Desforges, Marc; Coupanec, Alain Le; Brison, Élodie; Meessen-Pinard, Mathieu; Talbot, Pierre J.

doi:10.1007/978-81-322-1777-0_6

Cited by 259 publications

(312 citation statements)

References 114 publications

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“…MERS-CoV is one of the human corona viruses that include also five other strains: SARS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL-63, and HCoV-HKU1. Although corona viruses are generally known for causing respiratory illness, both clinical and experimental studies have demonstrated their strong tropism to the CNS [9][10][11][12][13][14][15]. SARS-CoV infection induced in mice model results in neuronal death without encephalitis [16].…”

Section: Discussionmentioning

confidence: 99%

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)

et al. 2015

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BackgroundSince the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection.MethodsData was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU.FindingThe three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement.InterpretationCNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed.Electronic supplementary materialThe online version of this article (doi:10.1007/s15010-015-0720-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)

et al. 2015

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“…In the human airways, HCoV infection may lead to the disruption of the nasal epithelium [250] and, although they bud and are released mostly on the apical side of the epithelial cells, a significant amount of viruses is also released from the basolateral side [251]. Thus, although HCoV infections are, most of the time, restricted to the airways, they may under poorly understood conditions pass through the epithelium barrier and reach the bloodstream or lymph and propagate towards other tissues, including the CNS [33,38,208,252]; this was also suggested for other respiratory viruses that can reach the human CNS, namely, RSV [8,53] [14,220,[252][253][254][255][256]] to manipulate the innate immunity and to disseminate to other tissues, including the CNS, where they may be associated with other type of pathologies, especially in immunocompromised individuals as it was observed for murine cytomegalovirus (MCMV) [257,258]. Moreover, persistently-infected leukocytes [252] may serve as a reservoir and vector for neuroinvasive HCoV [245].…”

Section: Possible Mechanisms Of Hcov Neuroinvasivenessmentioning

confidence: 99%

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

Desforges

Coupanec

Dubeau

et al. 2019

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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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“…These viruses have also been associated with lower respiratory tract illness in children, elders, and immunodeficient individuals (Falsey et al, 2002;Fouchier et al, 2004;Woo et al, 2005;Gerna et al, 2006). HCoV-229E and HCoV-OC43 may lead to central nervous system infection since viral RNAs are detected in the brain of some patients (Arbour et al, 2000;Desforges et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

et al. 2020

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Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptorbinding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.

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Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans

Cited by 259 publications

References 114 publications

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)

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

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

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