Arenaviruses

The Arenaviridae family (Latin arena - sand) consists of one genus, including over a dozen antigenically related representatives. Four of them cause severe diseases, usually accompanied by hemorrhagic syndrome: lymphocytic choriomeningitis (LCM), Lassa fever, Junin and Machupo.

Arenaviruses vary in shape (round, oval, polymorphic) and size (50-300 nm), but are predominantly round in shape and have an average diameter of 110-130 nm. They are surrounded by a dense membrane on which closely adjacent superficial processes, or villi, are located without visible symmetry, often club-shaped, about 10 nm long. The most characteristic morphological feature of the family is the presence of electron-dense granular structures inside the virus particles, resembling sand inclusions, which is reflected in the name of the family. These inclusions are the ribosomes of the host cells, are located circularly, especially in large virus particles, and are sometimes connected by thin delicate fibers.

The arenavirus genome is represented by 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 probably originate from the ribosomes of host cells. The virions contain transcriptase, which synthesizes a complementary RNA strand that functions as mRNA; reproduction occurs in the cytoplasm, and virion maturation occurs on cell membranes.

Arenaviruses, like all lipid-enveloped viruses, are inactivated by lipid solvents and detergents. They easily lose infectivity when heated, especially in the presence of divalent cations, in alkaline (pH above 8.5) and acidic (pH below 5.5) environments. They are sensitive to UV and gamma rays. They are well preserved in frozen and lyophilized conditions. They are capable of reproducing in chicken embryos and in the body of rodents of various ages, depending on the type of arenavirus. Of the cell cultures, the most sensitive to arenaviruses is the green monkey kidney cell culture (Vero); the viruses actively reproduce in it and form plaques under the agar coating.

Arenaviruses do not have hemagglutinating properties, but have a complement-fixing soluble antigen that can be detected in the CSC, immunofluorescence reaction and is identical to the internal antigen of the virion. Due to this antigen, cross-reactions between different arenaviruses are possible. Using indirect immunofluorescence using immune sera of guinea pigs and hamsters and immune ascitic fluids of mice, two antigenic groups of arenaviruses are detected - Old World viruses (LHM and Lassa fever) and New World viruses (Machupo and Junin viruses). The neutralization reaction is characterized by high specificity and allows identifying individual types of viruses.

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Immunity

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

Symptoms of Arenavirus Infections

Lymphocytic choriomeningitis is widespread almost everywhere, including Russia. Lymphocytic choriomeningitis is a zoonotic disease. The main host of the virus is gray house mice, sometimes Syrian hamsters and voles. Humans can become infected from infected animals through aerosols and alimentary routes, as well as through the bites of gamasid mites. The virus has a direct damaging effect on humans. It multiplies in the lymph nodes, from where it spreads throughout the reticuloendothelial tissue (the mononuclear phagocyte system), causing damage to capillaries, impaired permeability, and extensive hemorrhages. The incubation period is 6-7 days; clinically, lymphocytic choriomeningitis occurs as a flu-like disease, sometimes with a picture of aseptic meningitis or meningoencephalitis. It is accompanied by leukopenia 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 the savannas south of the Sahara (Nigeria, Liberia, Sierra Leone). The main reservoir of the virus is the polymammary rat Mastomys natalensis, which excretes large amounts of the virus in the urine. The virus is transmitted by contact from person to person (during outbreaks), from animals by airborne, alimentary means, and infection through damaged skin is possible. All this causes the occurrence of nosocomial and family outbreaks, diseases of medical personnel. The Lassa virus is one of the most dangerous for humans, working with it requires the strictest precautions. The pathogenesis is the same as with lymphocytic choriomeningitis, 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 increases, hemorrhagic diathesis, ulcerative pharyngitis, stomach pains appear, later - swelling of the face and neck, effusion in the abdominal and pleural cavities and in the pericardium. Mortality is on average about 43%, during individual epidemic outbreaks - up to 67%.

Bolivian hemorrhagic fever (Machupo) is a natural focal fever found in the northeastern Bolivian provinces of Manora and Itenez. The virus persists in the body of a mouse-like rodent - the hamster Calomys callosus, from which it is transmitted to humans through water and food contaminated with the rodent's urine. Infection by airborne droplets is also possible in the first days of the disease through contact with a sick person, when the virus is released from the upper respiratory tract. The incubation period is 7-14 days. The clinical picture of the disease consists of signs inherent in other hemorrhagic fevers, a feature is tremors of the limbs and tongue, proteinuria; hair loss and brittle nails are observed during the recovery period. The prognosis is favorable, but in individual outbreaks, the mortality rate reaches 30%. Deep changes in various organs are found in the deceased, especially in the liver (hemorrhages, areas of parenchyma necrosis).

Argentine hemorrhagic fever (Junin) is a disease occurring in central Argentina (the provinces of Buenos Aires, Cordoba and Santa Fe), where up to 3.5 thousand cases are registered annually. The reservoir and source of the Junin virus are the rodents Calomys musculinus and Calomys laucha; the virus can also be isolated from their exoparasites. Rodents have a persistent infection, and the virus is excreted in urine for a long time and in large quantities. Humans become infected by inhaling dust or by eating food contaminated by rodents. Transmissible infection is possible. The incubation period is 7-16 days. The onset is gradual: signs of intoxication increase, from the 5th day - hemorrhagic diathesis. The disease occurs against the background of impaired renal function, nervous and cardiovascular systems. The outcome is generally favorable, although mortality can sometimes reach 10-20%.

Laboratory diagnostics of arenavirus infections

When using virological and biological methods to isolate viruses, nasopharyngeal washes, blood, cerebrospinal fluid, urine, pleural effusion, and autopsy material are used as material. The choice of test object for infection is determined by the pathogenicity of the suspected pathogen for laboratory animals (white mice, guinea pigs, monkeys of various ages; brain infection is used), as well as by the different sensitivity of cell cultures to it. Vero cells, human amnion, and mouse embryos (cytopathic effect with intracellular inclusions, plaque formation) are most often used. Viruses are identified in the CSC, neutralization reaction, or indirect immunofluorescence.

The most accessible methods of serological diagnostics are the indirect immunofluorescence reaction (antibodies appear earlier and persist longer), as well as the complete immunofluorescence test and the immunofluorescence assay.

Treatment of arenavirus infections

There is no specific treatment for most arenavirus infections. The only effective treatment for Lassa fever is the use of hyperimmune serum from recovered or immunized individuals. Serum from convalescents should be used with caution, as the virus may persist in the blood for several months after acute infection.

Specific prevention of arenavirus infections

For prevention, the use of live attenuated vaccines is promising; they should primarily be used to immunize medical and laboratory workers, as well as individuals who come into contact with rodents.