What is the neurotropic potential of coronaviruses?

Coronaviruses are large RNA viruses with a genome of more than .30,000 nucleotides and involved, in humans, in almost a third of acute infections of the respiratory tract. Because of their complexity and the mildness of the symptoms caused, they remain bad known and rarely researched in diseases

There is however a murine model neurological damage by coronavirus with induction immunity against the basic protein of myelin and demyelination recalling the signs of multiple sclerosis.

In addition, a small five amino acid fragment of a human coronaviral protein is identical to a motif of the basic protein of human myelin, located near areas recognized by lymphocytes from patients with multiple sclerosis. Coronaviruses are finally one of the viruses identified (due to the presence of viral particles or antibodies) in this condition.

All of these clues should stimulate research on this species of virus and its possible role in serious human diseases with demyelenization, primarily multiple sclerosis.

Coronaviruses are still too often absent from the medical literature, which undeniably reflects a lack of work and knowledge on this subject. First
isolated in the mid-sixties from patients with colds, it is now recognized that human coronaviruses are responsible for 15 to 35% of acute respiratory tract infections, the clinical symptoms being able to be reproduced experimentally in volunteers.

The main other infectious agents associated with this type of disease are the rhinoviruses and the para-influenza and influenza viruses. From childhood, the vast majority of the population has seroconversion to coronaviral antigens, which highlights the high prevalence of infections caused by these apparently endemic viruses. The diseases that are currently attributed to them, although mild, nevertheless cause significant economic losses.

In addition, the medical significance of coronaviruses may be more
great that what our still superficial knowledge about this family of viruses and the absence of appropriate diagnostic tools allow us to assess at present.

A seroepidemiological study suggests, for example, their involvement in the etiology of more serious diseases such as certain pneumonias and peryocarditis, and perhaps meningitis and radiculitis. Other observations of enteric coronaviruses associated with certain severe gastroenteritis, especially in newborns and children less than a year old, must be confirmed.

Finally, coronaviruses are on the long list of potential contributors to multiple sclerosis (MS), an autoimmune demyelinating disease that develops in people who are genetically predisposed, following exposure to an environmental factor. still unknown. The neurological implication of coronaviruses remains largely to be demonstrated. Coronaviriform particles were, however, observed in sections of brains and coronaviruses isolated from patients with SEP.

In addition, anticoronavirus antibodies have been detected frequently, and in high titers, in the cerebrospinal fluid of patients with MS. Furthermore, the histological localization of antigens coronavirals in the brains of infected mice are reminiscent of the histopathology of post-encephalitic parkinsonian syndrome or Parkinson’s disease.

It should be noted, moreover, that human coronaviruses share with a multitude of other viruses the property of being at the origin of persistent infections, which suggests the possibility of a pathogenic process with slow development.

Ubiquitous, coronaviruses are a family of structurally and functionally related pathogens. Their involvement in more or less debilitating diseases of the respiratory tract, the gastrointestinal tract or the central nervous system in several mammals and volatiles, should therefore provide us with valuable clues for the study of coronaviral pathogenesis in human beings.

Structure and replication


Coronaviruses are a family of enveloped viruses, including spaced and shaped surface projections, or peplomers bulbs, give a characteristic appearance of a crown encircling viral particles, hence their name proposed in 1 968.

Some coronavirus, one of which is known to have two human serotypes, a second fringe of smaller peplomers which are associated with haemagglutinating activity, facilitating the detection of viruses, but whose biological function remains unknown.

Most of our knowledge of the molecular structure, biology and pathogenesis of coronaviruses comes from work carried out on murine corona viruses.

Genome and proteins:

 With more than 30,000 nucleotides, the viral genome represents the longest known RNA. Its particular mode of replication generates a high frequency of recombination. The sequence nucleotide of the genome of a murine coronavirus suggests, for example, that hemagglutinin found in certain coronaviruses would have been acquired during a coinfection with a strain of the influenza virus.

Furthermore, a recombination between coronaviral and cellular genes would be conceivable. Finally, the replication of such a long RNA molecule gives rise to mutations which also contribute to genetic variability. All this suggests the adaptive capacity of coronaviruses and worries about the possibility of the appearance of variants whose pathogenic power could
be increased or changed to benefit the virus.

Three or four structural proteins make up the virions. On the one hand, the N protein which is used to encapsulate the genomic RNA and, on the other hand, two or three glycoproteins which are inserted into the viral envelope ravished to the infected cell during of the morphogenesis of virions. The membrane glycoprotein M seems to play an essentially structural role. The surface glycoprotein S forms the viral peplomers.

It is therefore involved in the attachment of viral particles to receptors present on the surface of susceptible cells, the carcinoembryonic antigen appearing to constitute a privileged target. Protein S also plays a key role in viral propagation by cell fusion, following its insertion in the cytoplasmic membrane of infected cells. In several coronaviruses, this fusion activity is induced by the proteolytic cleavage of the molecule.

This cleavage occurs differently depending on the type of cell involved, which could influence the pathogenesis as in the case of measles viruses and acquired immunodeficiency in humans. Certain coronaviruses, including one of the two human serotypes, also have a third glycoprotein, called HE for its haemagglutinating and esterase.

The biological function of this protein remains unknown. Finally, with the exception of an RNA-dependent RNA polymerase, the function of the four or cmq non-structural proteins of the coronavirus is unknown.