This study investigates the virological and immunological features of hepatitis C virus (HCV) infection in five healthcare workers who were accidentally exposed to HCV-positive blood. The subjects were followed weekly for 6 months, and the results provide insights into the host-virus relationship during the incubation phase of acute HCV infection. Key findings include: 1. **Viremia and T Cell Response**: Viremia was detectable within 1-2 weeks of inoculation, often before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged acute hepatitis episode coinciding with a CD38+ IFN-γ+ CD8+ T cell response and a small reduction in viremia. 2. **Chronic Infection**: Two subjects developed chronic infection due to a lack of significant T cell response, while another two initially mounted strong CD4+ T cell responses that waned over time. 3. **Virological and Immunological Characteristics**: The study provides the first detailed description of asymptomatic acute HCV infection and highlights the importance of the early T cell response in determining the outcome of infection. It suggests that the vigor and quality of the antiviral T cell response are crucial for viral clearance. 4. **Pathogenesis and Viral Clearance**: The onset of hepatitis coincides with the onset of the CD8+ T cell response, and disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations using both cytolytic and noncytolytic mechanisms. 5. **Viral Persistence**: Different pathways to viral persistence exist in asymptomatic and symptomatic acute HCV infection, and the ability of HCV to outpace the T cell response may contribute to its persistence. The study emphasizes the dynamic interplay between the virus and the host, suggesting that HCV infection can trigger multiple etiologically related but pathogenetically different diseases, posing significant challenges for immunotherapeutics and vaccines.This study investigates the virological and immunological features of hepatitis C virus (HCV) infection in five healthcare workers who were accidentally exposed to HCV-positive blood. The subjects were followed weekly for 6 months, and the results provide insights into the host-virus relationship during the incubation phase of acute HCV infection. Key findings include: 1. **Viremia and T Cell Response**: Viremia was detectable within 1-2 weeks of inoculation, often before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged acute hepatitis episode coinciding with a CD38+ IFN-γ+ CD8+ T cell response and a small reduction in viremia. 2. **Chronic Infection**: Two subjects developed chronic infection due to a lack of significant T cell response, while another two initially mounted strong CD4+ T cell responses that waned over time. 3. **Virological and Immunological Characteristics**: The study provides the first detailed description of asymptomatic acute HCV infection and highlights the importance of the early T cell response in determining the outcome of infection. It suggests that the vigor and quality of the antiviral T cell response are crucial for viral clearance. 4. **Pathogenesis and Viral Clearance**: The onset of hepatitis coincides with the onset of the CD8+ T cell response, and disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations using both cytolytic and noncytolytic mechanisms. 5. **Viral Persistence**: Different pathways to viral persistence exist in asymptomatic and symptomatic acute HCV infection, and the ability of HCV to outpace the T cell response may contribute to its persistence. The study emphasizes the dynamic interplay between the virus and the host, suggesting that HCV infection can trigger multiple etiologically related but pathogenetically different diseases, posing significant challenges for immunotherapeutics and vaccines.