Hepatitis E virus

The hepatitis E virus (HEV) has a spherical shape, diameter 27-34 nm, the type of symmetry of the nucleocapsid is icosahedral, there is no outer shell.

Hepatitis E virus was identified in the feces of patients who transferred viral hepatitis "neither A nor B" by enteral infection, as well as in feces of experimental animals (monkeys) infected with the same virus-containing material by means of immune electron microscopy (IEM) using serums of convalescents of this hepatitis.

To date, it has been established that the hepatitis E virus has the following physico-chemical and biological characteristics.

• Morphologically it is represented by spherical particles, which lack shells; on their surface there are thorns and impressions; the virus disintegrates by exposure to CS CL, freezing / thawing, stored at -20 ° C. 
• The diameter of the virus particles is from 32 to 34 nm.
• The genome is represented by RNA of 7.5 kb in length, single-stranded, polyadenylated.
• The sedimentation coefficient is equal to 183 S (for defective virus-like particles - 165 S). The floating density is 1.29 g / cm ³ in the gradient KTa / Glu.
• In vitro cultivation was unsuccessful.
• Intracerebral injection of a suspension of fecal extract containing HEV particles to suckling mice does not cause a disease in them.

With molecular cloning, large amounts of HEV were obtained from the bile of infected monkey macaque monkeys. The identity of viral particles derived from fecal extracts from hepatitis E patients in various regions of the world (Somalia, Borneo, Pakistan, Central Asia, etc.) was shown. The structure of the genome NEV has been practically deciphered. By analyzing the nucleotide sequences and organization of the genome, the difference between HEV and picornaviruses was established and it was shown that it can not belong to caliciviruses (saliviruses), as was originally supposed.

The genome is a single-stranded unfragmented positive RNA of 7,500 bases, contains three open reading frames encoding virus-specific proteins. On the surface of the virion there are impressions resembling bowls (Greek calyx), therefore the virus was originally included in the family Caliciviridae (genus Hepavirus). A more detailed study of the HEV genome has shown that the nucleotide sequence of its RNA is unique and has only some resemblance to the rubella virus.

Currently, HEV is classified as a member of the Nereviridae family, the genus Nerevirus, the hepatitis E.

The antigen (s) HEV-HEV Ag was identified on the surface of the virus particles by means of immune electron microscopy, in hepatocytes by immunohistochemical methods. In experimental animals (macaques and chimpanzees), who were infected with hepatitis E, HEV Ag was detected in the cytoplasm of hepatocytes with the help of immunofluorescent method when layering the liver sera from the same animals obtained in the period of convalescence; further, the specificity of HEV Ag was confirmed in absorption studies using recombinant proteins obtained by cloning the HEV genome.

In immunomorphological studies in hepatitis E-infected monkeys, the granular deposits of HEV Ag were localized in the cytoplasm of hepatocytes, with the beads with HEV Ag disorganized, and the number of granules varied significantly in different cells. There was no preferred localization of HEV-positive hepatocytes in any zone of the hepatic lobe. Hepatitis containing NEV Ag was constantly detected before the increase in ALT activity, then persisted during the entire period of hyperfermentemia and practically disappeared after the normalization of ALT activity.

Genomic sequences of HEV have been identified in feces, bile and serum of patients with human hepatitis E and experimental animals (monkeys); The humoral immune response from the acute stage of the disease to reconvalescence was studied.

The highest concentration of HEV particles was detected in the bile of infected macaques before the peak of ALT activity in the infection stage when the peak of the presence of HEV Ag in the liver was recorded.

RNA NEV was found in samples of feces, bile and sera from sick people and infected primates.

The presence of specific antibodies (anti-HEV) in patients with human hepatitis E and experimental animals in blood serum was determined by means of immune electron microscopy and the fluorescent antibody method using as substrate the preparations of HEV particles or hepatic sections containing HEV Ag.

Further cross-sectional studies of HEV isolates and sera from convalescent patients from different geographic regions where flares or sporadic cases of hepatitis E occurred, as well as those obtained from these primates infected with HEV particles and sera, finally convinced the researchers that there is one virus (or class of serologically related viruses), responsible worldwide for precisely hepatitis E.

The genotypic diversity of the virus is shown. Eight genotypes of the virus were identified, whose main prototypes were the following isolates: 1 genotype - NE isolate from Burma, 2 - from Mexico, 3 - from the USA 4 - from Taiwan and China, 5 - from Italy, 6 - from Greece, 7 - from Greece (second isolate), 8 - from Argentina.

It was shown that in the acute stage of hepatitis E in the macaques and chimpanzees in the blood serum, anti-HEV classes of IgM and IgG circulate, while in the sera of the reconvalescence period, anti-HEV of the class

In a number of studies in people with hepatitis E, the presence of anti-HEV IgM class was found in 73% of cases in the first 26 days of jaundice; In the same period of convalescence, 90% of patients showed anti-HEV IgG.

The source of infection is only a person, the pathogen is excreted with feces. The mechanism of infection is fecal-oral. The main way of infection is through contaminated water. The infecting dose compared to the hepatitis A virus is much higher. Susceptibility to the HEV virus is universal. Epidemics can reach tens of thousands of people with drinking disorders, especially during seasonal work in summer and autumn.

Clinically, hepatitis E proceeds more easily than hepatitis A, there is no transition to the chronic form. In 85-90% of patients, hepatitis E is mild to moderate in severity, often asymptomatic. However, in pregnant women, hepatitis E is severe - with a mortality rate of up to 20%.

For the diagnosis use the method of immune electron microscopy; A test system for the detection of antibodies to HEV antigens was proposed. Post-infectious immunity is strong, lifelong, caused by viral neutralizing antibodies and immune memory cells. For a specific prevention, a whole-virion vaccine is proposed and live and recombinant vaccines are developed.

[1], [2], [3], [4], [5], [6], [7], [8], [9],