Alpha viruses

Alpha viruses have a genome represented by single-stranded positive linear RNA with a molecular weight of 4.2 MDa. Virions are spherical, 60-80 nm in diameter. The genomic RNA is covered with a capsid consisting of 240 molecules of C-protein, the symmetry type is cubic, the shape of a regular delta-icosahedron (20 faces). A bilayer lipid membrane is located on top of the capsid, into which 240-300 glycoprotein complexes are embedded, penetrating the lipid membrane. They consist of 2-3 proteins (El, E2, sometimes E3). Membrane proteins interact with the C-protein, due to which they fasten the membrane to the nucleocapsid. Glycosylated parts of membrane proteins are always on the outer side of the lipid bilayer; complexes of these proteins form 10 nm long spikes protruding outward from the surface of the virion.

Alpha viruses include 21 serotypes; according to RTGA, neutralization reaction and radioimmune precipitation, they are divided into three antigen groups:

1. Western equine encephalomyelitis virus complex (including Sindbis virus);
2. Eastern equine encephalomyelitis virus complex;
3. Semliki Forest virus complex; some viruses are outside the groups.

Alpha viruses have the following antigens: species-specific supercapsid glycoprotein E2 - antibodies to it neutralize the infectivity of the virus; group-specific supercapsid glycoprotein E1 (hemagglutinin); genus-specific - nucleocapsid protein C. The hemagglutinating properties of alpha viruses, like all togaviruses, are better manifested in relation to bird, especially goose, erythrocytes.

To penetrate the cell, the virus uses the following route: adsorption of the virus by spikes (protein E2) on the protein receptors of the cell, then - bordered pit - bordered vesicle - lysosome. Having entered the lysosome, the virus avoids the danger of being digested due to the special properties of the proteins of its outer shell. These proteins facilitate the fusion of adjacent lipid bilayers at acidic pH values inside the lysosome. And as soon as the virus is in the lysosome, its outer shell "melts" with the lysosome membrane, which allows the nucleocapsid to enter the cytoplasm.

Alphaviruses replicate in the cytoplasm of the cell. When the nucleocapsid is "undressed", the genomic RNA is translated on ribosomes, and virus-specific RNA polymerase is formed. Transcription of alphaviral RNA occurs as follows: first, a complementary negative RNA strand is synthesized, and then many copies of RNA of two sizes are synthesized on it: virion RNA 42S and the smaller RNA 26S. Synthesis of 42S RNA is initiated from the 3'-end, and the complete chain of 42S RNA is transcribed. 26S RNA is produced independently, the initiation of its transcription begins from the second initiation site, located at a distance of 2/3 of the length from the 3'-end, and continues to the 5'-end of the template molecule. RNA 42S is a virion RNA and is used to assemble new nucleocapsids and also codes for the synthesis of non-structural proteins. RNA 26S serves as a matrix directing the synthesis of four structural proteins: capsid C-protein and envelope proteins El, E2, E3. Each of these RNAs is translated into a large polypeptide, which is sequentially subjected to cascade cleavage. The synthesis of envelope proteins occurs on membrane-bound ribosomes of the rough endoplasmic reticulum, and the capsid protein is synthesized on free ribosomes of the cytosol.

Next, the newly synthesized capsid protein joins the replicated copies of the genomic RNA, which leads to the formation of nucleocapsids. The proteins of the outer shell are incorporated into the membrane of the endoplasmic reticulum and are glycosylated there, then transported to the Golgi complex, where they undergo additional glycosylation, and then transferred to the cytoplasmic membrane. Passing through it, nucleocapsids are enveloped by a section of the membrane highly enriched in proteins of the outer shell, which are embedded in the lipids of the host cell. Next, the nucleocapsid buds off in such a way that, separating from the cell surface, it ends up surrounded by a closed supercapsid.

Flaviviruses are similar to alpha viruses in many ways and, according to the previous classification, were included in the togavirus family as an independent genus. The genomic RNA is single-stranded, linear, positive, its molecular weight is 4.0-4.6 MD. The diameter of the spherical virions is 40-50 nm, sometimes 25-45 nm ( tick-borne encephalitis virus ). The structure of the virions is not fundamentally different from that of alpha viruses, but the capsid protein of flaviviruses has a lower molecular weight (13.6 kD instead of 30-34 kD), and the spikes always consist of two proteins, only one of which is glycosylated (E1) and has hemagglutinating activity.

According to the results of the RPGA, all flaviviruses (about 50 serotypes) are divided into 4 subgroups: tick-borne encephalitis, Japanese encephalitis (including West Nile fever), yellow fever and dengue fever. An important feature of flaviviruses is the presence of a soluble antigen with type-specific activity in the RSC; this is a non-structural protein that is formed in infected cells during reproduction. Intracellular reproduction of flaviviruses is slower than that of alpha viruses, but goes through the same stages with some differences: only one class of mRNA is detected in infected cells - 45S; replication of virion RNA occurs on the nuclear membrane, and maturation of the virion occurs by budding through the membranes of the endoplasmic reticulum.

Alphaviruses are inactivated by proteases, while flaviviruses are resistant to them.

Togaviruses are unstable at room temperature, but survive at -70 °C. They are easily inactivated by ether and sodium deoxycholate. They are pathogenic for various animals, the infection is easily reproduced in mice during intracerebral infection. Newborn mice are especially susceptible. In sensitive vertebrate hosts, primary virus reproduction occurs in myeloid, lymphoid tissue or in the vascular endothelium. Reproduction in the CNS depends on the ability of the virus to cross the blood-brain barrier and infect nerve cells. Viruses reproduce in the chicken embryo when infecting the yolk sac or allantoic cavity. They reproduce well in monkey kidney cell cultures and chicken embryo fibroblasts, causing focal fine-grained degeneration.

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Symptoms of diseases caused by alpha viruses

After penetration through the skin by a carrier bite, the virus enters the bloodstream or lymphatic vessels. The primary site of reproduction of most togaviruses is the vascular endothelium and reticuloendothelial cells of the lymph nodes, liver, and spleen. After a 4-7 day incubation period, the virus enters the blood. Many infections have a second phase - local reproduction of the virus in selected organs: liver, brain, kidneys. The first phase is accompanied by leukopenia, the second - leukocytosis. The disease usually occurs suddenly, its onset coincides with the release of the pathogen into the blood.

An invariable symptom is fever, accompanied by headache, myalgia, aching joints, nausea, often a small-point rash and enlarged lymph nodes. In a significant number of cases, clinical manifestations are limited to the period of virus dissemination, followed by recovery without consequences. Fever may be complicated by hemorrhagic symptoms caused by vascular disorders. Bleeding of the mucous membranes and hemorrhagic rash appear. Fever may have a two-wave course: after a short remission, fever and new symptoms (albuminuria, jaundice, meningeal symptoms, encephalitis, myelitis) reappear, indicating damage to various organs.