Hepatitis E virus

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

The hepatitis E virus was identified in the feces of patients who had non-A, non-B viral hepatitis via the enteral route of infection, as well as in the feces of experimental animals (monkeys) infected with the same virus-containing material, using immune electron microscopy (IEM) using serum from convalescents of this hepatitis.

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

• Morphologically, it is represented by spherical particles without a shell; their surface has spikes and depressions; the virus disintegrates when exposed to CS CL, freezing/thawing, and is preserved at -20 °C.
• The diameter of viral particles is from 32 to 34 nm.
• The genome is represented by RNA 7.5 kb long, single-stranded, polyadenylated.
• The sedimentation coefficient is 183 S (for defective virus-like particles - 165 S). The buoyant density is 1.29 g/cm3 ⁱⁿ the KTa/Glu gradient.
• In vitro cultivation was unsuccessful.
• Intracerebral administration of a suspension of fecal extract containing HEV particles to suckling mice does not cause disease in them.

Using molecular cloning, large quantities of HEV were obtained from the bile of infected macaque monkeys. The identity of viral particles obtained from fecal extracts of hepatitis E patients in various regions of the world (Somalia, Borneo, Pakistan, Central Asia, etc.) was demonstrated. The structure of the HEV genome was practically deciphered. By analyzing the nucleotide sequences and genome organization, it was established that HEV differs from picornaviruses and that it cannot belong to the caliciviruses (caliciviruses), as was initially assumed.

The genome is represented by a single-stranded non-fragmented positive RNA of 7500 bases, contains three open reading frames encoding virus-specific proteins. On the surface of the virion there are depressions resembling cups (Greek calyx), therefore the virus was initially included in the Caliciviridae family (genus Hepavirus). A more detailed study of the HEV genome showed that the nucleotide sequence of its RNA is unique and has only some similarity with the rubella virus.

HEV is currently classified as a member of the Hepereviridae family, Heperevirus genus, hepatitis E virus.

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

In immunomorphological studies of hepatitis E-infected monkeys, granular deposits of HEV Ag were localized in the cytoplasm of hepatocytes, with granules containing HEV Ag being located randomly and the number of granules varying significantly in different cells. No preferential localization of HEV Ag-positive hepatocytes in any particular zone of the liver lobule was detected. Hepatitis containing HEV Ag was constantly detected before the increase in ALT activity, then persisted throughout the entire period of hyperenzymemia and virtually disappeared after normalization of ALT activity.

HEV genomic sequences were identified in feces, bile, and blood serum of patients with hepatitis E in humans and experimental animals (monkeys); the humoral immune response was studied from the acute stage of the disease to convalescence.

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

HEV RNA has been found in fecal, bile, and serum samples from infected humans and primates.

The presence of specific antibodies (anti-HEV) in the blood serum of patients with hepatitis E in humans and experimental animals was established using immune electron microscopy and the fluorescent antibody method using HEV particle preparations or liver sections containing HEV Ag as a substrate.

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

Genotypic diversity of HEV is shown. Eight genotypes of the virus were identified, the main prototypes of which were the following isolates: genotype 1 - HEV 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 has been shown that in the acute stage of hepatitis E in macaques and chimpanzees, anti-HEV classes IgM and IgG circulate in the blood serum, while in the sera of the convalescence period, only anti-HEV class

In a number of studies, anti-HEV IgM was detected in 73% of patients with hepatitis E in the first 26 days from the onset of jaundice; during the recovery period, anti-HEV IgG was detected in 90% of patients.

The source of infection is only humans, the pathogen is excreted with feces. The mechanism of infection is fecal-oral. The main route of infection is through water contaminated with feces. The infectious dose is significantly higher than that of the hepatitis A virus. Susceptibility to the HEV virus is universal. Epidemics can affect tens of thousands of people if the drinking regime is violated, especially during seasonal work in summer and autumn.

Clinically, hepatitis E is milder than hepatitis A, and transition to a chronic form has not been noted. In 85-90% of patients, hepatitis E is mild or moderate, often asymptomatic. However, in pregnant women, hepatitis E is severe, with a mortality rate of up to 20%.

Immune electron microscopy is used for diagnostics; a test system for detecting antibodies to HEV antigens has been proposed. Post-infection immunity is strong, lifelong, and is due to virus-neutralizing antibodies and immune memory cells. A whole-virion vaccine has been proposed for specific prophylaxis, and live and recombinant vaccines are being developed.

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