HCV structure and genotypes

HCV structure and genotypes

HCV structure and genotypes

On this page

HCV Structure - The Viral Blueprint

image

  • Family: Flaviviridae.

  • Genome: Enveloped, single-stranded, positive-sense RNA (+ssRNA).

  • Translation: Utilizes an Internal Ribosome Entry Site (IRES) for cap-independent translation within the host cell cytoplasm.

  • Proteins Encoded: A single polyprotein is cleaved into:

    • Structural Proteins: Form the virion.
      • Core (C): Capsid protein.
      • Envelope (E1, E2): Glycoproteins for entry.
    • Non-Structural (NS) Proteins: For replication.
      • NS2 to NS5B: Includes protease, helicase, and RNA-dependent RNA polymerase (NS5B), a key drug target.

⭐ The high variability of the E2 glycoprotein's Hypervariable Region 1 (HVR1) is a key mechanism for immune evasion and persistence.

HCV Genotypes - A Diverse Family

  • Genetic Heterogeneity: HCV is classified into 6 major genotypes (1-6) and numerous subtypes (e.g., 1a, 1b), which differ by >30% at the nucleotide level.

    • Genotype 1 is the most common in the United States.
  • Quasispecies Concept: The virus exists as a dynamic swarm of related but distinct variants in a single patient.

    • This arises because the viral RNA-dependent RNA polymerase (NS5B) is error-prone and lacks proofreading capacity.
    • This genetic diversity allows the virus to evade the host immune system and contributes to the development of antiviral resistance.

Genotype 3 is most strongly associated with the development of hepatic steatosis and has a higher risk of accelerated fibrosis and hepatocellular carcinoma (HCC).

Clinical Relevance - Why Genotypes Matter

HCV genotyping is critical for tailoring antiviral therapy and maximizing cure rates (SVR). The choice between pangenotypic and genotype-specific regimens hinges on the specific viral genotype identified.

  • Treatment Guidance: Genotype determines the optimal Direct-Acting Antiviral (DAA) regimen and duration.
  • Pangenotypic Regimens: Effective across all major genotypes (1-6).
    • Examples: Glecaprevir/Pibrentasvir, Sofosbuvir/Velpatasvir.
    • Simplifies the treatment decision process, especially when testing is unavailable.
  • Resistance: Pre-existing Resistance-Associated Substitutions (RASs) can lead to DAA failure. RAS testing may be considered, especially in treatment-experienced patients.

⭐ The presence of cirrhosis, prior treatment history, and specific genotype are the three most critical factors guiding the selection and duration of modern DAA regimens.

  • HCV is an enveloped, single-stranded, positive-sense RNA virus from the Flaviviridae family.
  • Lacks a proofreading 3'-5' exonuclease in its RNA polymerase (NS5B), leading to high mutation rates.
  • This genetic instability results in multiple quasispecies within a single host, aiding immune evasion.
  • There are at least 6 major genotypes; Genotype 1 is the most common in the U.S.
  • Genotype is crucial for predicting response to and guiding the choice of direct-acting antiviral (DAA) therapy.

Practice Questions: HCV structure and genotypes

Test your understanding with these related questions

A 28-year-old woman with a history of intravenous drug use is brought to the emergency department because of a 1-day history of fatigue, yellow eyes, confusion, and blood in her stools. She appears ill. Her temperature is 38.1°C (100.6°F). Physical examination shows pain in the right upper quadrant, diffuse jaundice with scleral icterus, and bright red blood in the rectal vault. Further evaluation demonstrates virions in her blood, some of which have a partially double-stranded DNA genome while others have a single-stranded RNA genome. They are found to share an identical lipoprotein envelope. This patient is most likely infected with which of the following pathogens?

1 of 5

Flashcards: HCV structure and genotypes

1/10

Why does HCV have a lack of proofreading ability and thus displays antigenic variation?_____

TAP TO REVEAL ANSWER

Why does HCV have a lack of proofreading ability and thus displays antigenic variation?_____

lack of 3'-5' exonuclease

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial