Molecular Virology

Rotavirus infection at the molecular level

Rotavirus infects duodenal enterocytes, leading to their massive destruction. A key pathogenicity factor is the nonstructural viral protein NSP4. It functions as an enterotoxin and triggers secretory diarrhea. The disease is accompanied by vomiting, abdominal pain, and frequent stools (up to 10–15 times per day) lasting 1–2 days. The infection is especially dangerous for children aged 6 months to 2 years due to the risk of mortality from dehydration.

To detect the pathogen, a stool filtrate is used, where the virion concentration reaches colossal values ($10^{10}$ particles per microliter). The diagnosis is confirmed by virological methods (immune electron microscopy, ELISA, IFA), molecular genetic methods (RT-PCR), or serologically by a rise in antibody titers at 3–8 weeks. Specific prevention is provided by live oral vaccines from attenuated strains.

Molecular markers of viral hepatitis B (HBV)

Hepatitis B diagnostics is based on the detection of specific antigens, antibodies, and viral DNA. Quantitative assessment of viremia and genotyping are critically important for choosing treatment tactics.

• HBsAg is the surface antigen, the earliest indicator of virus presence, appearing as early as the incubation period.
• HBeAg is a marker of active replication and high contagiosity. If it circulates for more than 2–3 months without the appearance of antibodies, the risk of chronization is high.
• HBcAg is the core antigen. It is not detected in peripheral blood without hepatocyte cytolysis; it is found exclusively in liver tissue.
• anti-HBc IgM is the most reliable indicator of the acute phase of infection, disappearing after 4–6 months.
• anti-HBe and anti-HBs are markers of a favorable prognosis, seroconversion, and recovery.
• HBV DNA and DNA polymerase are direct markers of replication. Viral DNA is detected by PCR 1–3 weeks earlier than HBsAg.

Assessment of severity and co-infection in hepatitis

When acute liver failure develops (fulminant form of hepatitis B), the most important laboratory criterion is the prothrombin index (PI). Its drop to less than 40% is a direct indication for initiating etiotropic therapy.

Additionally, the severity of the condition is confirmed by "bilirubin-protease dissociation"—a sharp drop in transaminase levels against the background of growing jaundice and coagulopathy, which indicates massive liver necrosis rather than improvement. Hypoalbuminemia, hypoglycemia, elevated ammonia levels, and signs of DIC syndrome are also observed. The biochemical marker of the thymol turbidity test in hepatitis B remains low, which helps distinguish it from hepatitis A and E.

An important rule: in all patients with positive HBsAg, antibodies to hepatitis D virus (anti-HDV) must be checked by ELISA or viral RNA by PCR, as superinfection radically changes the course of the disease.

Principles of antiviral therapy

The main goal of chronic hepatitis B treatment is to suppress viral replication with its subsequent eradication.

1. Interferons (IFN-α) are the drugs of choice in pediatrics. They bind to cellular receptors and, through the Jak-STAT cascade, induce the synthesis of antiviral proteins, as well as activate NK cells and cytotoxic T lymphocytes. They are prescribed in the presence of viral DNA, a twofold increase in ALT, and signs of fibrosis. The standard course in children lasts 6 months, with the first response assessment performed at 3 months.
2. Nucleoside/nucleotide analogues are reverse transcriptase inhibitors. Entecavir has a high resistance barrier and is taken strictly on an empty stomach. Tenofovir (TDF/TAF) is taken with food. The dosages of these drugs require strict adjustment depending on the glomerular filtration rate (GFR). Lamivudine is not recommended in modern practice due to the rapid development of viral resistance.

Antiviral therapy is also indicated for patients with extrahepatic manifestations of the infection (vasculitis, glomerulonephritis, polyarthritis) with confirmed viral replication.

Class and exam questions

What else to study on this topic

• Serological diagnostics of rotavirus infection and antibody titer dynamics
• Biochemical criteria for the severity of fulminant hepatitis (ammonia, hypoglycemia, coagulopathy)
• Mechanism of action of pegylated interferons and the Jak-STAT immune cascade
• Extrahepatic manifestations of chronic viral hepatitis B
• Indications for emergency and planned hospitalization in viral hepatitis

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