Twincore View Institution's Website 1 article published in JoVE Immunology and Infection Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors Anne Frentzen*1, Kathrin Hueging*1, Julia Bitzegeio2, Thomas Pietschmann1, Eike Steinmann1 1Division of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, 2Aaron Diamond AIDS Research Center, Laboratory of Retrovirology, The Rockefeller University, NY We describe two methods for conditional trans-complementation of hepatitis C virus (HCV) assembly and the completion of the full viral life cycle, which rely on heterokaryon formation. These techniques are suitable to screen for cell lines that express dominant restriction factors, which preclude production of infectious HCV progeny.