PROTEIN SIGNALING MOLECULES AFFECTING THE DEVELOPMENT OF INNATE IMMUNITY MECHANISMS

The principle protein molecules (interferon gene stimulator, adapter proteins, B-cell lymphoma 2 proteins, zinc-finger antiviral protein, and others), mechanisms of apoptosis, necroptosis, perforation of plasma membranes with kinase-like proteins of a mixed line, and ribonucleic acid neutralization, which ensure the development of innate immunity, are described. The main defense mechanisms that viruses have developed at the various stages of evolution are considered. The features of the development of the mechanisms of apoptosis and autophagy in a new coronavirus infection, which are associated with increased secretion of pro-inflammatory cytokines and chemokines, leading to severe damage to host cells, are given. It has been found that serum levels of several proteins formed during autophagy caused by SARS-CoV-2 can be used to predict disease severity. These include a protein associated with microtubules 1A/1B, a protein of sequestoma 1, and a protein of the cellular system of autophagy ― beclin-1. The multifaceted role of interferons in the inhibition of viral infection and the features of the violation of the activating functions of interferons in coronavirus infection are described. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

Features of immunopathogenesis of a new coronavirus infection

The main biological characteristics of viruses of the Coronaviridae family are presented. The features of the immunopathogenesis of these infections are analyzed. It was found that the structural proteins of the spine, membrane, envelope and nucleocapsid play an important role in the immunopathogenesis of COVID-19 infection. They are associated with hyperactivation of neutrophils and monocytes-macrophages, secreting large amounts of pro-inflammatory cytokines and chemokines. This contributes to the development of a left-pointing-double-angle cytokine storm right-pointing-double-angle and an unfavorable prognosis of the disease. A particularly high risk of developing pneumonia exists against the background of an increase in the production of: macrophage inflammatory protein-1 alpha, macrophage chemotactic protein, interleukin 8. At the height of infection in some patients, macrophages and dendritic cells infected with SARS-CoV-2 lose their ability to produce type I interferons and pro-inflammatory cytokines. On the part of cellular immunity, a significant decrease in the number of CD4+ and CD8+-lymphocytes was noted. Among IgG sub-isotypes, IgG3 antibodies had the highest reactivity, and IgG1 antibodies were less reactive. Antibodies to spike protein with low specificity or low titer do not neutralize the virus and contribute to the contamination of immunocompetent cells via Fc receptors. Low-affinity antibodies or their low levels can contribute to increased cell sensitivity to SARS-CoV-2 and the development of severe forms of COVID-19 disease.

Old new coronavirus

The main biological characteristics of Coronaviridae viruses, including viruses, severe acute respiratory syndrome and Middle East respiratory syndrome, are presented. The features of immunopathogenesis associated with these infections and their differences from the infection 2019-2020 are analyzed. It is believed that the modern incidence of upper respiratory tract in adults, associated with coronaviruses, is between 10 and 30%. Coronaviruses are ecologically diverse, with the greatest diversity in bats, suggesting that they are the main reservoirs of coronaviruses. Research into the genome of the new coronavirus - 2019-nCoV has shown that it has about 80% nucleotide identity with original viruses of severe acute respiratory syndrome and the ability to bind to angiosine-transforming receptors enzyme 2. This, along with the high genetic proximity of coronaviruses, indicates their overall origin and overall probable source. However, the receptors of the angiosin-transforming enzyme 2 are the key that gives access to the cell even with low infecting activity. It has been shown that the main diagnostic methods to increase the specificity of detection of a new coronavirus should be variants of polymerase chain reaction and immunoblotting. However, there is still a lot of unknown related to the life of the 2019-nCoV virus. There is a clear identification and comparison of the genomes of the virus in different countries. Identify those genetic inserts that allow the virus to escape from the control of the immune system and turn into a hypervirulent strain. Proving or disprove the possibility of the 2019-nCoV virus is altering its genetic and antigenic potential in different animal species and becoming a new type of virus.