title: CHD6 chromatin remodeler is a negative modulator of influenza virus replication that relocates to inactive chromatin upon infection.
abstract: The influenza virus establishes close functional and structural connections with the nucleus of the infected cell. Thus, viral ribonucleoproteins (RNPs) are closely bound to chromatin components and the main constituent of viral RNPs, the nucleoprotein (NP) protein, interacts with histone tails. Using a yeast two-hybrid screening, we previously found that the PA influenza virus polymerase subunit interacts with the CHD6 protein, a member of the CHD family of chromatin remodelers. Here we show that CHD6 also interacts with the viral polymerase complex and colocalizes with viral RNPs in the infected cells. To study the relationships between RNPs, chromatin and CHD6, we have analysed whether NP and CHD6 binds to peptides representing trimethylated lysines of histone 3 tails that mark transcriptionally active or inactive chromatin. Upon infection, NP binds to marks of repressed chromatin and, interestingly an important recruitment of CHD6 to these heterochromatin marks occurs in this situation. Silencing experiments indicate that CHD6 acts as a negative modulator of influenza virus replication. Hence, the CHD6 association with inactive chromatin could be part of a process where the influenza virus triggers modifications of chromatin-associated proteins that could contribute to the pathogenic events used by the virus to induce host cell shut-off.
authors: Centro Nacional de Biotecnología. Darwin 3, Cantoblanco, 28049 Madrid, Spain.
authors: Roberto
authors: R
authors: Alfonso
authors: Thomas
authors: T
authors: Lutz
authors: Ariel
authors: A
authors: Rodriguez
authors: J Pablo
authors: JP
authors: Chavez
authors: Paloma
authors: P
authors: Rodriguez
authors: Silvia
authors: S
authors: Gutierrez
authors: Amelia
authors: A
authors: Nieto
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D020868:Gene Silencing; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002843:Chromatin; D006657:Histones; D009419:Nerve Tissue Proteins; C061290:PA protein, influenza viruses; D012261:Ribonucleoproteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase; D004265:DNA Helicases; C471926:CHD5 protein, human