Hepatitis C virus (HCV) is a small enveloped, positive‑sense, single‑stranded RNA virus of the Hepacivirus genus (Flaviviridae family) that causes hepatitis C, a liver disease transmitted mainly through blood‑to‑blood contact.
Genome and Replication
HCV’s positive‑sense RNA genome is about 9.6 kb long and encodes a single polyprotein that is cleaved by host and viral proteases into structural proteins (core and envelope glycoproteins E1 and E2), the p7 ion channel and nonstructural proteins (NS2, NS3/4A serine protease, NS4B, NS5A and NS5B RNA‑dependent RNA polymerase). The virus attaches to hepatocytes through interactions with receptors such as CD81, scavenger receptor class B type 1, claudin‑1 and occludin. Entry occurs via clathrin‑mediated endocytosis and fusion within endosomes. Translation of the viral RNA occurs at the endoplasmic reticulum, producing the polyprotein. Nonstructural proteins remodel intracellular membranes to form a membranous web where replication takes place. The error‑prone NS5B polymerase generates high genetic diversity, leading to seven genotypes and numerous subtypes. Assembly of nucleocapsids occurs on lipid droplets, and mature virions are secreted via the very‑low‑density lipoprotein pathway. HCV replication is facilitated by host factors, including microRNA‑122, which stabilises the viral genome. Chronic infection reflects the virus’s ability to evade innate and adaptive immune responses through mechanisms such as interfering with interferon signaling.
Clinical Impact and Treatment
HCV infection is often clinically silent in its acute phase; however, around 55–85% of infected individuals develop chronic hepatitis, which can progress over decades to fibrosis, cirrhosis and hepatocellular carcinoma. According to the World Health Organization, there are approximately 58 million people living with chronic HCV infection globally, with about 1.5 million new infections occurring each year. The virus is primarily transmitted through exposure to contaminated blood, notably via injection drug use or unscreened blood transfusions before the early 1990s. Screening of blood products and safe injection practices have reduced new infections in many countries. Six major genotypes influence geographic distribution and treatment response. The advent of direct‑acting antiviral drugs targeting NS3/4A protease, NS5A and NS5B polymerase has revolutionized therapy, achieving sustained virologic response rates exceeding 95% with short, well‑tolerated regimens. Despite these advances, there is still no approved vaccine, and challenges remain in diagnosis, access to treatment and prevention of reinfection.
Hepatitis C virus is a hepatotropic flavivirus with a compact genome that encodes a polyprotein processed into structural and nonstructural components. Its capacity for chronic infection and high genetic variability make it a major global health concern. While curative therapies exist, efforts to expand testing, treatment and harm‑reduction strategies are essential to achieve elimination goals.
Related Terms: Hepatitis B virus, Flaviviridae, NS5A inhibitor, Cirrhosis, Liver cancer