Arenaviruses

The family Arenaviridae (Latin arena - sand) consists of one genus, which includes more than a dozen antigenically related representatives. Four of them cause severe diseases, usually with hemorrhagic syndrome: lymphocytic choriomeningitis (LXM), Lassa fever, Junin and Machupo fevers.

Arenaviruses vary both in shape (rounded, oval, polymorphic), and in size (50-300 nm), but they are mostly rounded and have an average diameter of 110-130 nm. Surrounded by a dense shell, on which are located closely adjacent to each other surface processes, or villi, often clavate, about 10 nm in length, without apparent symmetry. The most characteristic morphological feature of the family is the presence of electron-dense granular structures inside the viral particles resembling sandy inclusions, which is reflected in the family name. These inclusions are ribosomes of host cells, are located circularly, especially in large virus particles, and are sometimes connected by thin, delicate fibers.

The genome of arenaviruses is represented by a single-stranded linear negative RNA, consists of five fragments, two of which are virus-specific (with a molecular weight of 3.2 and 1.6 MD), and the rest are probably derived from ribosomes of host cells. The composition of virions includes transcriptase, which synthesizes a complementary strand of RNA functioning as mRNA; reproduction occurs in the cytoplasm, virion maturation - on the cell membranes.

Arenaviruses, like all lipid-containing viruses, are inactivated by fat solvents and detergents. Easily lose infectivity when heated, especially in the presence of divalent cations, in alkaline (pH above 8.5) and acidic (pH below 5.5) media. Sensitive to UV and gamma rays. Well preserved in the frozen and freeze-dried state. Capable of multiplying in the chick embryo and in the body of rodents of different ages, depending on the type of arenavirus. Of the cell cultures, the culture of kidney cells of green monkeys (Vero) has the highest sensitivity to arenaviruses; viruses actively multiply in it and form plaques under an agar coating.

Arenaviruses do not have haemagglutinating properties, but they have a complement-binding soluble antigen that can be detected in the DSC, an immunofluorescence reaction, and is identical to the internal virion antigen. Due to this antigen, cross reactions between different arenaviruses are possible. With the help of indirect immunofluorescence with the use of immune sera guinea pigs and hamsters and immune ascitic fluids in mice, two antigenic groups of arenaviruses are identified - Old World viruses (LXM and Lassa fevers) and New World (Macupo and Junin viruses). The neutralization reaction is characterized by high specificity and allows identifying specific types of viruses.

[1], [2], [3], [4], [5], [6], [7]

Immunity

Arenavirus infections are characterized by the accumulation of antibodies, the dynamics of which are well studied. Antibodies, determined by the method of indirect immunofluorescence, usually appear on the 2-3 nd week. Disease, when the patient's condition begins to improve, and in many cases, IgA antibodies are found. Complement-binding and viral neutralizing antibodies can be detected much later.

Symptoms of arena virus infections

Lymphocytic choriomeningitis is widespread almost everywhere, including in Russia. Lymphocytic choriomeningitis - zooanthroponosis. The main host of the virus is gray house mice, sometimes Syrian hamsters and voles. A person can be infected from infected animals by aerosol and alimentary route, and also through the bites of gamasid mites. A direct damaging effect of the virus is observed in humans. It multiplies in the lymph nodes, from where it spreads throughout the reticuloendothelial tissue (the system of mononuclear phagocytes), causing damage to the capillaries, impaired their permeability and extensive hemorrhages. The incubation period is 6-7 days; clinically lymphocytic choriomeningitis occurs as an influenza-like disease, sometimes with a picture of aseptic meningitis or meningoencephalitis. It is accompanied by leuko- and thrombocytopenia. As a rule, it proceeds favorably and ends with complete recovery. There is evidence of a possible teratogenic effect of the LHM virus on the fetus during intrauterine infection.

Lassa fever is an endemic infection of savannahs to the south of the Sahara (Nigeria, Liberia, Sierra Leone). The main reservoir of the virus is the multi-nosed rat Mastomys natalensis, which releases a large amount of the virus in the urine. The virus is transmitted by contact from person to person (during outbreaks), from animals by aerogenic, alimentary route, possibly through contaminated skin. All this causes the emergence of nosocomial and family outbreaks, diseases of medical personnel. Lassa virus is one of the most dangerous for a person, working with him requires the strictest precautions. Pathogenesis is the same as with lymphocytic chorio meningitis, but with a predominant lesion of internal organs. The incubation period is 7-8, sometimes up to 20 days. The onset of the disease is gradual: intoxication, hemorrhagic diathesis, ulcerative pharyngitis, stomach pain, later - edema of the face and neck, effusion into the abdominal and pleural cavity and pericardium. Mortality is on average about 43%, during individual epidemic outbreaks - up to 67%.

Bolivian hemorrhagic fever (Machupo) is of a natural focal character, found in the northeastern provinces of Bolivia Manora and Itenes. The virus persists in the body of a mouse-like rodent - a hamster called Calomys callosus, from which it is transmitted to a person through water and food contaminated with the urine of a rodent. It is also possible to get airborne infection in the first days of illness when contacting a patient when the virus is released from the upper respiratory tract. The incubation period is 7-14 days. The clinic of the disease consists of the signs inherent in other hemorrhagic fevers, a peculiarity is the trembling of limbs and tongue, proteinuria; during the recovery period, hair loss and brittle nails are observed. The prognosis is favorable, but in certain outbreaks, lethality reaches 30%. Deceased persons show profound changes in various organs, especially in the liver (hemorrhages, parenchyma necrosis areas).

Argentine haemorrhagic fever (Junin) is a disease that occurs in the central part of Argentina (the province of Buenos Aires, Cordoba and Sao Ta Fe), where up to 3,500 cases are recorded annually. The reservoir and source of the Junin virus are the rodents Calomys musculinus and Calomys laucha; the virus also can be isolated from their exo-parasites. In rodents, a persistent infection is observed, and the virus is long and massive secreted with urine. A person becomes infected by inhalation of dust or by eating foods contaminated with rodents. It is not excluded the transmission path of infection. The incubation period is 7-16 days. The onset is gradual: there are signs of intoxication, from the 5th day - the phenomenon of hemorrhagic diathesis. The disease occurs against a background of impaired renal function, nervous and cardiovascular systems. The outcome is generally favorable, although lethality can sometimes reach 10-20%.

Laboratory diagnosis of arena virus infections

When virological and biological methods are used to isolate viruses, washings from the nasopharynx, blood, liquor, urine, pleural effusion, sectional material are used as a material. The choice of the test object for infection is determined by the pathogenicity of the suspected pathogen for laboratory animals (white mice, guinea pigs, monkeys of different ages, infection is used in the brain), and also the sensitivity of cell cultures to it. More often used Vero cells, human amnion, embryo mice (cytopathic effect with intracellular inclusions, plaque formation). Identify viruses in the DSC, neutralization reaction or indirect immunofluorescence.

The most accessible methods of serological diagnosis are indirect immunofluorescence (antibodies appear in earlier periods and last longer), as well as DSC and RPGA.

Treatment of arena virus infections

For most arenavirus infections, no specific treatment has been developed. The only effective method of treating Lassa fever is the use of hyperimmune serum from people who are ill or immunized. Serum from convalescent should be used with caution, since the virus can persist in the blood for several months after an acute infection.

Specific prophylaxis of arena virus infections

For prevention, the use of live attenuated vaccines is promising, which must first of all be immunized by medical and laboratory workers, as well as persons in contact with rodents.