Chronic hepatitis B and C virus infections are major causes of liver disease and hepatocellular carcinoma worldwide. Although both viruses infect hepatocytes, the molecular virology and cellular biology of their respective replication cycles differ. Viral entry is the first step of the life cycle and recent developments in functional genomic and proteomic methodologies have increased our understanding of the entry pathways for these two important human pathogens. In this review we provide a comparative analysis of the internalization routes for these viruses and highlight differences and how they impact the viral life cycle, immune responses and development of antivirals.
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