HCV Core Antigen Specific Neutra™ Antibody Products

Hepatitis C virus (HCV) is an enveloped RNA virus, causing chronic liver disease and increasing the risk of cirrhosis and liver cancer. The genome of HCV encodes a variety of structural and non-structural proteins. The virus particles consist of a lipid bilayer and a core protein. The core antigen (HCVcAg) is a key component of the viral nucleocapsid, that is cleaved from polyproteins by a signal peptidase. HCV exhibits significant genetic diversity, with eight major genotypes and numerous subtypes, which influences treatment strategies and outcomes for infected individuals.

Fig. 1 HCV genome structure with the core protein delineated.^{1, 3}

Role of HCVcAg in Virus Replication

HCVcAg is vital for virus replication. Synthesized on ER membranes and then dimerized, it translocates to lipid droplets (LDs), crucial for virion assembly. Core protein accumulation on LDs, mediated by its C-terminal amphipathic helices, alters LD distribution, clustering them near the nucleus. This interaction is dynamic; core protein movement to LDs and subsequent release, forming puncta, is essential for new particle formation. Paradoxically, excessive core protein on LDs hinders infectious particle production, suggesting transient LD association. Host factors like DGAT1, PLA2G4, and IKK-α modulate core protein-LD interactions, influencing viral assembly. AP2M1 facilitates core protein release from LDs, though the mechanism remains complex.

HCVcAg as Marker for Active Infection

HCVcAg serves as a valuable diagnostic marker for active HCV infection due to its early appearance compared to antibodies and its specific expression during active infection, distinguishing it from past infections. It remains reliable in immunosuppressed individuals. HCVcAg's strong correlation with HCV RNA levels, coupled with its ease of use, faster processing, and lower cost, makes it a potential alternative to RNA testing. The combination of HCVcAg and antibody serology improves early detection and treatment monitoring. While serum and plasma are preferred, studies show consistent correlations across diverse patient groups, including transplant recipients and those with co-infections. Current guidelines support HCVcAg assays as a confirmation test for active infection.

HCVcAg as a Tool for Diagnostic Testing and Treatment Monitoring

HCVcAg is a versatile biomarker used in various immunoassays, such as EIAs, CIAs, and LFAs, aiding in active HCV infection detection, especially where NAT is limited. Highly sensitive aptamer-based assays also exist. For treatment monitoring, HCVcAg levels decline faster than HCV RNA post-treatment initiation, though correlations vary during treatment. Baseline and post-treatment correlations are strong, supporting HCVcAg's utility. High concordance rates and kappa indices reinforce its role. While WHO guidelines don't specify HCVcAg for direct-acting antivirals monitoring, EASL suggests undetectable levels post-treatment can indicate SVR, particularly in resource-limited settings, crucial for HCV elimination goals.

Fig. 2 Summary of HCV testing and treatment.^{1, 3}

Anti-HCVcAg Neutralizing Antibodies

HCVcAg plays a crucial role in the virus life cycle and pathogenesis, making it an ideal target for antibodies. Sequestering HCVcAg can disrupt core particle assembly and RNA packaging while also affecting cell proliferation and lipid metabolism. As one of the most conserved HCV proteins, antibodies targeting its conserved epitope can potentially impact a broad range of viral isolates across different genotypes. Anti-HCVcAg antibodies are also used in diagnostic tests like ELISA to detect active HCV infections. Specific, cross-reactive monoclonal antibodies with strong binding properties have been developed for detecting HCVcAg in infected samples. In another study, phage display-derived scFvs from chronic hepatitis C patients reduced intracellular core protein levels and reversed core protein-induced cell proliferation.

Fig. 3 The double antibody sandwich ELISA for HCVcAg detection.^{2, 3}

Creative Biolabs provides high-quality anti-HCVcAg neutralizing antibody products to accelerate your viral infection detection.

REFERENCES

1. Le, Duong Hoang Huy, et al. "Hepatitis C Virus—Core Antigen: Implications in Diagnostic, Treatment Monitoring and Clinical Outcomes." Viruses 16.12 (2024): 1863.
2. Vidal-Alcántara, Erick Joan, et al. "Production and characterization of monoclonal antibodies for the detection of the hepatitis C core antigen." Frontiers in Molecular Biosciences 10 (2023): 1225553.
3. Distributed under Open Access license CC BY 4.0, without modification.