The pathogenesis of coronaviral infection in little is known about humans and the immune defense mechanisms against it. Local destruction of the hair epithelial cells, as a result of their infection with the coronavirus, most likely contributes to the development of respiratory and possibly gastrointestinal diseases.
The inoculation of volunteers made it possible to show the importance of circulating and local antibodies, the latter being of the IgA type, in alleviating the symptoms and eliminating the virus. It seems that the antibodies neutralizers are directed against viral peplomers.
The immune destruction of infected cells could involve a mechanism of antibody-dependent cell cytotoxicity. Unfortunately, coronaviral infection produces only specific immunity of the viral strain involved and antigenic heterogeneity, even within a single serotype, promotes several consecutive infections.
Nasal administration of interferon, on the other hand, seems more promising for reducing the duration and severity of coronaviral colds than for reducing rhinoviral infections…
Animal models of coronaviral infections provide us with valuable information on the biology of these viruses. The rat coronavirus produces rhinotracheitis accompanied by mild localized interstitial pneumonia and cellular infiltration.
The avian infectious bronchitis virus also causes respiratory disease, but the infection quickly spreads to the reproductive system and kidneys of chicken. Furthermore, a murine coronaviral strain induces immunosuppression in animals, associated with replication of the virus in B and T lymphocytes.
However, the animal model that leaves the most pensive about the medical importance of these viruses is that of coronaviral infection of the central nervous system of mice and rats. Neurotropic strains of the murine coronavirus indeed cause neurological diseases which have pathological characteristics similar to those encountered in human diseases such as MS.
These experimental models allow the dissection of the molecular determinants of the disease and the analysis of the interactions between the virus and the immune system.
Adult mice infected with a neurotropic murine coronavirus usually develop encephalomyelitis accompanied by infection of glial and neuronal cells. There is then more than 95% mortality. The few animals that survive this acute disease have white matter disease characterized by the appearance of demyelination plaques in the brain and spinal cord, followed by remyelination and then recurrent demyelination.
Two different pathological processes could explain the development of this type of demyelinating disease. It could be, on the one hand, the infection and destruction of oligodendrocytes, the cells responsible for the synthesis of the myelin sheath (viral antigens are also detected in these cells for at least a year ). It could, on the other hand, be an autoimmune attack on the central nervous system resulting viral infection.
This last hypothesis is reinforced by the observation of a sensitization to the basic protein of the myelin (PBM) of the lymphocytes of the infected animals which reveals the appearance of an experimental allergic encephalomyelitis after the adoptive transfer of these cells to animals not infected. This autoimmune disease can be reproduced experimentally by injecting PBM. In addition, immunosuppressive therapy prevents the development of viral-induced demyelination in mice.
Finally, it has recently been demonstrated that coronaviral particles can induce the expression of class I and II histocompatibility antigens on glial cells of the central nervous system, which suggests the activation, at this level, of immune responses. cell-mediated. In animals, various types of viral mutants induce a modified pathological process in which the oligodendrocytes are infected and the neurons spared.
This disease, characterized by chronic and recurrent demyelination rather than by lethal encephalitis, is also observed after the passive transfer of certain monoclonal antibodies or CD4 + lymphocytes.
It appears that complete elimination of viral infection requires CD4 + and CD8 + lymphocytes. In addition, in mice, genetic factors determine susceptibility to coronaviral disease, and several autosomal recessive genes controlling resistance have been identified.
The importance of glycoprotein S in virulence, as well as in tropism and induction of a response protective immune system, is no longer in doubt. Neutralizing monoclonal antibodies specific for certain antigenic S protein sites passively protect against coronaviral encephalitis. It is also possible to prepare an effective antiidiotypic vaccine consisting of antibodies produced against a protective monoclonal antibody.
A subunit vaccine consisting of purified protein S and a vaccine Synthetic consisting of a decapeptide coupled to a carrier molecule can also protect mice from disease.
In addition, an essential region as a target of protective immunity, and whose conservation on several viral strains suggests the biological importance, has been localized precisely on p rotein S.
Finally, much less virulent mutants of altered tropism, apparently resulting from modifications of this key protein of coronaviral biology, could be isolated under the selective pressure of certain neutralizing monoclonal antibodies specific for specific antigenic sites on protein S Other viral proteins most likely play an important role in virus-host interactions.
Certain monoclonal antibodies directed against the glycoprotein M can, for example, neutralize the viral infection in vitro in the presence of complement, and even protect against encephalitis in vivo. Protein N may also represent the target of protective antibodies, and it is conceivable, by analogy with other viral infections, that it participates in the induction of a cell-mediated immune response.