Since its discovery in 1989, Hepatitis C Virus (HCV) has challenged clinicians and researchers due to its ability to establish chronic infection and its silent progression toward liver cirrhosis and hepatocellular carcinoma. Earlier treatments based on interferon were often poorly tolerated and ineffective for many genotypes. The advent of direct-acting antivirals (DAAs) has transformed the landscape, enabling cure rates exceeding 95%. However, vertical transmission—mother-to-child transmission during gestation or delivery—remains a neglected route, with a 2025 Lancet study estimating over 74,000 new pediatric cases annually.

Fig. 1. Estimated annual number of HCV infections through vertical transmission in each country or territory*HCV=hepatitis C virus. *Point estimates.（10.1016/S2468-1253(25)00189-X）

Virion Structure and Genomic Organization

The Hepatitis C Virus (HCV) is a complex enveloped RNA virus characterized by a spherical virion structure, featuring a lipid envelope derived from the host cell membrane, which is embedded with glycoprotein complexes E1 and E2. These glycoproteins are critical for viral attachment and entry into hepatocytes. At the core of the virion lies a nucleocapsid composed of the core protein, encapsulating a single-stranded, positive-sense RNA genome of approximately 9.6 kilobases. This genome is highly organized, encoding a single open reading frame (ORF) flanked by untranslated regions (UTRs) that regulate translation and replication. Understanding the virion structure and genomic organization is essential for developing targeted therapeutics and diagnostics, as these elements dictate key processes such as viral entry, RNA replication, and immune evasion. The genome is translated into a polyprotein that is subsequently cleaved into structural proteins (core, E1, E2) and non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, NS5B), each playing distinct roles in the viral life cycle. 

Fig.2.Hepatitic C Virus Structure

Pathogenesis and Immune Evasion Strategies

Hepatitis C virus (HCV) primarily targets hepatocytes, the main functional cells of the liver, where it establishes persistent infections that may last for decades if untreated. One of the key reasons for this persistence is the virus’s extraordinary ability to evade the host immune system through rapid genetic variation. The viral RNA-dependent RNA polymerase (NS5B) lacks a proofreading mechanism, which results in a high error rate during viral replication. This leads to the formation of a quasi-species population—a swarm of genetically distinct but closely related viral variants within a single host. These variants allow HCV to continually escape recognition by neutralizing antibodies and cytotoxic T cells, undermining adaptive immune responses. In addition to genetic diversity, HCV employs active mechanisms to suppress innate immune signaling, thereby blunting the host's first line of defense. The viral NS3/4A protease cleaves key adaptor molecules such as MAVS (mitochondrial antiviral-signaling protein) and TRIF (TIR-domain-containing adapter-inducing interferon-β), effectively silencing type I interferon pathways that are essential for early antiviral responses. Meanwhile, NS5A, a multifunctional phosphoprotein, interferes with interferon-stimulated gene expression and modulates host cell lipid metabolism to facilitate viral replication. Over time, this persistent immune evasion leads to chronic inflammation in the liver, contributing to the development of fibrosis (the buildup of scar tissue), steatosis (abnormal fat accumulation in hepatocytes), and eventually cirrhosis or hepatocellular carcinoma (HCC). Chronic HCV infection is thus not only a viral disease but also a progressive immunopathological condition, driven by both viral factors and host immune dysregulation.

Vaccine Development: Barriers and Advances

Although DAAs are effective, a preventive vaccine is essential for elimination. Major barriers include genetic variability across genotypes and lack of robust models. Candidates such as INO-8000 and ChAd3/MVA NSmut vaccines are in clinical evaluation. Strategies include:

• Virus-like particles (VLPs) mimicking native virions
• Multi-epitope T cell vaccines targeting conserved NS regions
• mRNA-based platforms using E1/E2 or NS3/NS5A

Fig. 2. Timeline of vaccine strategy development (source: Genes Immun 20, 436–446 (2019).).

abinScience HCV-Related Products

Below is a list of abinScience’s HCV-related protein and antibody products. For more details, contact our dedicated advisors!

References