Alpha viruses

Alpha viruses have a genome represented by a single-stranded positive linear RNA with a molecular weight of 4.2 MD. Vyrions of spherical shape, diameter 60-80 nm. The genomic RNA is covered by a capsid consisting of 240 C-protein molecules, the symmetry type is cubic, the shape of the regular delta-icosahedron (20 facets). Over the capsid is a bilayer lipid membrane, in which 240-300 glycoprotein complexes are inserted, penetrating the lipid membrane. In their composition, 2-3 proteins (El, E2, sometimes E3). Membrane proteins interact with C-protein, so they bind the membrane to the nucleocapsid. The glycosylated portions of the membrane proteins are always on the outside of the lipid bilayer; complexes of these proteins form spines 10 nm long protruding outward from the surface of the virion.

Alpha viruses include 21 serotype; according to RTGA, neutralization and radioimmunity precipitation reactions are divided into three antigenic groups:

1. a complex of Western horse encephalomyelitis virus (including the Sindbis virus);
2. a complex of the virus of Eastern horse encephalomyelitis;
3. complex of the Semiliki forest virus; some viruses are outside the groups.

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

To penetrate into the cell, the virus uses the following pathway: the adsorption of the virus with spines (E2 protein) on the cell's protein receptors, then the fossa fringe-bordered vesicle-lysosome. The lysosomal virus avoids the danger of being digested due to the specific properties of the proteins of its outer shell. These proteins contribute to the fusion of adjacent lipid bilayers with acidic pH values within the lysosome. And once the virus is in the lysosome, its outer membrane "fuses" with the lysosome membrane, which allows nucleocapsid to enter the cytoplasm.

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

Further, the newly synthesized capsid protein is attached to replicated copies of genomic RNA, which leads to the formation of nucleocapsids. Outer envelope proteins are incorporated into the membrane of the endoplasmic reticulum and there are glycosylated, then transported to the Golgi complex, where they undergo additional glycosylation, and then transferred to the cytoplasmic membrane. Passing through it, the nucleocapsids are enveloped by a membrane region strongly enriched with outer envelope proteins that are embedded in the host cell lipids. Further, nucleocapsid budding occurs in such a way that, separating from the cell surface, it turns out to be surrounded by a closed supercapsid.

Flaviviruses are similar in many respects to alpha viruses and, according to the previous classification, as an independent genus, were part of the family of togaviruses. Genomic RNA is single-stranded, linear, positive, its molecular weight is 4.0-4.6 MD. The diameter of 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 in flaviviruses the capsid protein has a lower molecular weight (13.6 kD instead of 30-34 kD), and the spines consist of two proteins, only one of them is glycosylated (E1) and has hemagglutinating activity.

According to the results of 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, which has a type-specific activity in RSK; it is a non-structural protein that is formed in infected cells during reproduction. Intracellular reproduction of flaviviruses proceeds slower than alpha viruses, but passes through the same stages with some differences: in infected cells only one mRNA-45S class is detected; replication of the virion RNA occurs on the nuclear envelope, and the maturation of the virion goes by budding through the membranes of the endoplasmic reticulum.

Alpha viruses are inactivated by proteases, while flaviviruses are resistant to them.

Togaviruses are unstable at room temperature, but remain at -70 ° C. Easily inactivated by ether and sodium deoxycholate. Pathogens for various animals, the infection is easily reproduced in mice with intracerebral infection. Especially susceptible to newborn mice. In sensitive vertebrate hosts, the primary multiplication of the virus occurs in the myeloid, lymphoid or vascular endothelium. Reproduction in the CNS depends on the ability of the virus to pass through the blood-brain barrier and infect the nerve cells. Viruses multiply in a chicken embryo upon infection into the yolk sac or allantoic cavity. They reproduce well in cultures of kidney cells of monkeys and fibroblasts of chick embryos, causing focal fine-grained degeneration.

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Symptoms of diseases caused by alpha viruses

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

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