The influenza virus RNA-dependent RNA polymerase interacts with the serine-5 phosphorylated carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pot II). It was proposed that this interaction allows the viral RNA polymerase to gain access to host mRNA-derived capped RNA fragments required as primers for the initiation of viral mRNA synthesis. Here, we show, using a chromatin immunoprecipitation (ChIP) analysis, that similar amounts of Pot II associate with Pot II promoter DNAs in influenza virus-infected and mock-infected cells. However, there is a statistically significant reduction in Pot II densities in the coding region of Pot II genes in infected cells. Thus, influenza virus specifically interferes with Pot II elongation, but not Pot II initiation. We propose that influenza virus RNA polymerase, by binding to the CTD of initiating Pot II and subsequent cleavage of the capped 5' end of the nascent transcript, triggers premature Pot II termination. (c) 2006 Elsevier Inc. All rights reserved.