1977. mark of inactive chromatin, H3K27me3, remained unchanged. Our results indicate that CHD1 is a positive regulator of influenza virus multiplication and suggest a role for chromatin remodeling in the control of the influenza virus life cycle. IMPORTANCE Although influenza virus is not integrated into the genome of the infected cell, it needs continuous cellular transcription to synthesize viral mRNA. This mechanism implies functional association with host genome expression and thus depends on chromatin dynamics. Influenza virus polymerase associates with transcription-related factors, such as RNA polymerase II, and with chromatin remodelers, such as SU14813 CHD6. We identified the association of viral polymerase with another chromatin remodeler, the CHD1 protein, SU14813 which positively modulated viral polymerase activity, viral RNA transcription, and virus multiplication. Once viral transcription is complete, RNAP II is degraded in infected cells, probably as a virus-induced mechanism to reduce the antiviral response. CHD1 associated with RNAP II and paralleled its degradation during infection with viruses that induce full or reduced degradation. These findings suggest that RNAP II degradation and CHD1 degradation cooperate to reduce the antiviral response. INTRODUCTION Influenza A virus contains eight single-stranded RNA segments of negative polarity (viral RNA [vRNA]) that form viral ribonucleoproteins (vRNP) by association with a trimeric polymerase complex that consists of the PA, PB1, and PB2 subunits and the nucleoprotein (NP). These vRNP are the functional units for RNA transcription and replication, which are restricted to the nucleus of the infected cell (1). For viral RNA replication, the vRNAs are copied to form full-length positive-stranded RNAs (cRNA), which serve as templates for vRNA synthesis (2). During transcription, capped and polyadenylated viral mRNAs are synthesized by the SU14813 viral polymerase through an initiation mechanism that uses as primers short-capped oligonucleotides scavenged from newly synthesized RNA polymerase II (RNAP II) transcripts by a viral endonuclease activity that resides in the PA subunit (3, 4). This transcription strategy involves functional coupling between viral and cellular transcription for the cap-snatching process. The viral polymerase is reported to interact with host cell transcription-related factors (5,C9), among which is the largest subunit of the RNAP II itself (10). Although influenza virus does not integrate into the infected-cell genome, its transcription mechanism involves absolute dependence on chromatin-based functions and thus on chromatin dynamics. vRNP are tightly bound to the nuclear matrix or to chromatin components (11,C15), and viral RNA transcription and replication are proposed to take place in DNase-insensitive nuclear fractions that include chromatin and/or the cellular matrix (16). Specific interactions take place between chromatin remodelers and influenza virus proteins, including the association of CHD3 with the nonstructural protein NS2 (17). CHD6 interacts with the KCTD19 antibody PA polymerase subunit and with the viral polymerase complex (8, 18), which relocates to inactive chromatin late in infection (18) and negatively modulates influenza virus SU14813 multiplication (18). CHD3 and CHD6 belong to the CHD ((22) and cellular transcription. The Click-iT RNA Alexa Fluor 488 imaging kit enabled the detection of newly synthesized RNA (50) using an alkyne-modified nucleoside, the compound 5-ethynyluridine (EU), which is incorporated into RNA but not DNA. We also analyzed bromouridine (BrU) incorporation and RNAP II-Ser2P levels. Control-silenced or CHD1-silenced A549 cells either were.