Virion structure and genome features
The virus has a spherical shape with a complex organization. The virion diameter is 55–65 nm (while the core size is 70–80 nm).
- Capsid: Possesses an icosahedral type of symmetry. It includes a structural protein (core) forming the HCc antigen, as well as a number of non-structural protein enzymes (NS2, NS3, NS4, NS5) that are necessary for replication. Inside the capsid, it contains a nucleoprotein and the enzyme revertase (reverse transcriptase). It performs three functions: DNA transcription on an RNA template, DNA transcription on a DNA template, and nuclease activity.
- Supercapsid: Represents a lipoprotein envelope with glycoprotein spikes (gpE1, gpE2/NS1). Depending on the size, shape of the spikes, and core localization, 4 morphological types (A, B, C, D) are distinguished. Type C is the most common (found in mammals, birds, and fish).
The genetic apparatus is represented by a single-stranded linear positive-sense RNA. About 14 genotypes of the virus are known, among which genotype 1b is considered the most virulent. A key feature of the virus is high genome variability. The region encoding glycoproteins E1 and E2 (targets for antibodies) is extremely variable, which causes the hypermutability of the pathogen.
Epidemiology and stability
The infection is massively widespread: more than 1/3 of the world's population is infected. A relatively large infectious dose is required for transmission (higher than for the hepatitis B virus).
Main transmission routes:
- Blood transfusion — the leading route, accounting for 2/3 of all cases.
- Transplacental — from mother to fetus (about 10%).
- Sexual — accounts for approximately 7%.
In the environment, the virus is fragile: it is sensitive to heating up to 50 °C, UV radiation, ether, and detergents. The pathogen lacks hemolytic and hemagglutinating activity. It is extremely difficult to cultivate: it does not grow on chicken embryos and adapts with difficulty to cell cultures. The chimpanzee serves as the only experimental model for studying the infection.
Clinical course and pathogenesis
The incubation period is prolonged and varies from 6 to 120 weeks.
The acute phase of infection is noticeably milder than in hepatitis B and often takes anicteric forms. The main marker of this period in the blood is an elevated level of the enzyme alanine aminotransferase (ALT).
Despite the mild onset, the disease has a pronounced tendency to chronicity, which occurs in 50% of cases. Chronic hepatitis C often leads to the development of cirrhosis and primary liver cancer.
The high percentage of chronicity is explained by two main reasons:
- "Escape" phenomenon: due to constant genome mutations, the produced neutralizing antibodies cannot effectively block the virus.
- Absence of a strong cellular response: the target for CD4 lymphocytes is an epitope of the non-structural protein NS3 (common to all genotypes). When this immune link is weakened, the pathogen is reactivated.
It is hypothesized that the virus is capable of prolonged persistence in the lymph nodes within the body.
Diagnostics, treatment, and prevention
The main material for microbiological study is blood.
- PCR (polymerase chain reaction): Serves as the "gold standard" for early diagnosis because it detects the viral RNA itself. The test becomes positive within a few days after infection, clearly confirming the active process.
- ELISA (enzyme-linked immunosorbent assay): The paired sera method is used to search for antibodies. The method has an important drawback — the seronegative window. This is a period of several weeks when the virus is actively circulating and the blood is infectious, but antibodies to it have not yet been produced. Therefore, PCR remains the method of choice in clinical practice.
Specific prophylaxis (vaccine) has not been developed. Non-specific prophylaxis comes down to preventing parenteral and sexual routes of transmission. Combination antiviral therapy, including interferon preparations and ribavirin, is used to treat chronic hepatitis C.
Briefly: answers to topical questions
Which enzyme performs the synthesis of viral RNA during hepatitis C virus replication?
The synthesis of viral RNA during hepatitis C virus replication is carried out by RNA-dependent RNA polymerase. This non-structural enzyme synthesizes a complementary minus-strand using the genomic plus-strand RNA as a template. Subsequently, the resulting minus-strand serves as a template for the synthesis of new viral genomes (full copies of plus-strand RNA) and incomplete mRNA strands.
In which immune system cells is the hepatitis C virus capable of persisting and replicating?
The hepatitis C virus is capable of multiplying in lymphocytes, which leads to the disruption of their immunological function. Sources also indicate the persistence of HCV in monocytes as the main cause of graft reinfection in patients with severe forms of chronic hepatitis C after liver transplantation. In addition, prolonged persistence of the virus in the lymph nodes is suspected.
What modern classes of direct-acting antivirals (DAAs) are used for etiotropic therapy of hepatitis C?
Direct-acting antivirals are used for etiotropic therapy. Of the specific classes, only NS3/4A inhibitors are mentioned in the texts.
The following drug combinations are used in modern treatment regimens:
- Sofosbuvir and velpatasvir
- Glecaprevir and pibrentasvir
- Daclatasvir and sofosbuvir
- Ledipasvir and sofosbuvir
The rule of three "Cs" for hepatitis C: Concealed (often without jaundice), Mild (acute phase is milder than hepatitis B), Chronic-prone (50% of cases).
Class and exam questions
Why is there still no vaccine against the hepatitis C virus?
Creating a vaccine is difficult due to the high variability (hypermutability) of the viral genome. The regions encoding surface target proteins for antibodies (E1 and E2) are constantly changing.
What is the danger of the "seronegative window" in ELISA diagnostics?
During the "seronegative window" (the first few weeks after infection), antibodies in the blood are still absent, and the ELISA will give a negative result, even though a person's blood already contains the virus and is a source of infection.
What method should be used for the earliest possible diagnosis?
PCR is the method of choice. It allows the detection of viral RNA in the blood just a few days after infection.
What else to study on this topic
- Functions of non-structural proteins (NS2, NS3, NS4, NS5) and their role in replication.
- Mechanisms of viral revertase activity in HCV (transcription and nuclease function).
- Features of the interaction of the NS3 protein with CD4 lymphocytes.
- Mechanisms of persistence of the hepatitis C virus in lymph nodes.
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