Virology Pathogenic agents

What properties are you interested in?

@argentum Perhaps I'm more interested in the concept of pathogenic factors 🤨 

The pathogenic properties of viruses consist of the following components: - the ability of the virus to enter the body and adsorb on cell membranes, - to penetrate into cells sensitive to them; - the ability of these cells to deproteinize the viral genome and make it functionally active; -permissiveness of cells or the ability of these cells to provide transcription and replication of genetic material, complete assembly of virions; -the ability to reproduce in cells several cycles of viral reproduction, cytopathic action of the virus; the ability of viruses to spread to new cells located next to the affected; the spread of viruses outside the primary focus of the lesion throughout the body; -the ability to cause local and general pathological processes that underlie the clinical manifestations of the diseases they cause; -the ability of the virus to transfer to a new organism and ensure its relay transmission. All these properties are necessary, but at the same time, by themselves, they may not be sufficient for the pathogenic action of the virus. Some of these properties are due to the cells in which they multiply, which is called the host's cell restriction. Many viruses enter the body directly through the mucous membranes, which serve as the entrance gate of infection and are protected by a number of nonspecific resistance factors; therefore, viruses must be resistant to the action of these adverse factors, which is determined by the genes of the viruses. For example, intestinal viruses are usually resistant to acidic pH values, the detergent action of bile salts, and the destructive action of proteolytic enzymes. The ability of viruses to adsorb to the membranes of virus-sensitive cells is a specific process for viruses. This process takes place with the participation of attachment proteins (antireceptors) in viruses and cell receptors that are sensitive to them. Simple viruses contain attachment proteins in the capsid, and complex viruses in the super-capsid. Complex viruses such as vaccinia and herpes simplex virus can have several types of attachment proteins. The ability of viruses to adapt to a new host is due to a change in the primary structure in the region of the region of the attachment protein that recognizes the cell receptor. These areas are conservative in their structure and are located in canyon depressions, which are extremely small in size, due to which they are inaccessible to the active centers of antibodies that react only with the hypervariable regions surrounding these depressions, which allows viruses to avoid immunological pressure. Mutations in genes encoding antireceptors sometimes lead to a complete loss of the ability of viruses to interact with cellular receptors. By itself, the adsorption of viruses on the cell surface does not always lead to the penetration of viruses into cells. Many viruses with hemagglutinin on their surface are adsorbed on erythrocytes, especially on non-nuclear erythrocytes of mammals, but do not penetrate into them, since the latter are deprived of the ability to endocytosis. The same is largely true for the preserved nuclei of avian erythrocytes. But if, simultaneously with endocytosis, the fusion of cell and viral membranes does not occur during infection with complex viruses that have a supercapsid, and a similar interaction of the viral capsid with the cell membrane during infection with simple viruses, then endocytosis alone will not be enough, since the endocytic vacuole will become a "graveyard" for virions. This stage of interaction is extremely important and specific for different viruses. It involves special fusion proteins, which are found in many enveloped viruses, or their functional regions. Fusion proteins lead to dysfunction of cell membranes, a change in their permeability. Fusion proteins are not identical to the attachment proteins of viruses. The best studied fusion protein in paramyxoviruses is called F-protein (from the English fusion - fusion). The region of F proteins involved in fusion is highly conserved. Mutations in this region block the fusion process. Merging can take place from the outside and from the inside. With a high multiplicity of infection, fusion occurs from the outside, which appears almost immediately after infection and does not require the synthesis of virus-encoded proteins. Fusion from within is detected at low multiplicity of infection. It is caused by newly synthesized fusion proteins and appears in the later stages of the infectious process. For the manifestation of the infectious activity of viruses, post-translational processing of fusion proteins is required, which consists in proteolytic cutting of the precursor protein as a result of point or limited proteolysis, which leads to its activation and the formation of a fragment that interacts with the cell membrane. In this way, the fusion proteins of the viruses resemble the protoxins of bacteria.

These proteases can be of both cellular and viral origin. Mutations in the cutting site lead to blocking proteolysis and the production of non-infectious viruses that are unable to carry out multicyclic infection, so the infectious process will be abortive. The degree of proteolysis is of great importance for the generalization of viral infection in the body. Post-translational modification of viral proteins as a result of proteolytic cutting is a critical moment in the final acquisition of infectious activity by viruses and presents a vulnerable target for proteolysis inhibitors. Viral fusion proteins disable not only infected cells, but also non-virus infected cells that make up the syncytium. They make it possible for viruses to pass from cell to cell along the formed intercellular bridges, due to which viruses do not enter the intercellular space and become inaccessible for neutralizing antibodies.

@argentum Thanks for the complete answer 😀 

@benzol00 I was glad to help 👍