Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region.
In measles virus (MV)-infected cells, the ribonucleoprotein (RNP) complex, comprised of the viral genome and the nucleocapsid (N) protein, phosphoprotein (P protein), and large protein, assembles at the perinuclear region and synthesizes viral RNAs. The cellular proteins involved in the formation of the RNP complex are largely unknown. In this report, we show that cofilin, an actin-modulating host protein, interacts with the MV N protein and aids in the formation of the RNP complex. Knockdown of cofilin using the short hairpin RNA reduces the formation of the RNP complex after MV infection and that of the RNP complex-like structure after plasmid-mediated expression of MV N and P proteins. A lower level of formation of the RNP complex results in the reduction of viral RNA synthesis. Cofilin phosphorylation on the serine residue at position 3, an enzymatically inactive form, is increased after MV infection and the phosphorylated form of cofilin is preferentially included in the complex. These results indicate that cofilin plays an important role in MV replication by increasing formation of the RNP complex and viral RNA synthesis.


OBJECTIVE
Many RNA viruses induce within infected cells the structure called the ribonucleoprotein (RNP) complex in which viral RNA synthesis occurs. It is comprised of the viral genome and proteins that include the viral RNA polymerase. The cellular proteins involved in the formation of the RNP complex are largely unknown. In this report, we show that cofilin, an actin-modulating host protein, binds to the measles virus (MV) nucleocapsid protein and plays an important role in the formation of the MV RNP complex and MV RNA synthesis. The level of the phosphorylated form of cofilin, enzymatically inactive, is increased after MV infection, and the phosphorylated form is preferentially associated with the RNP complex. Our findings determined with cofilin will help us better understand the mechanism by which the RNP complex is formed in virus-infected cells and develop new antiviral drugs targeting the RNP complex.
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ritsuko
R
Koga
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Yukihiko
Y
Sugita
Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Takeshi
T
Noda
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan yyanagi@virology.med.kyushu-u.ac.jp soono@virology.med.kyushu-u.ac.jp.
Yusuke
Y
Yanagi
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan yyanagi@virology.med.kyushu-u.ac.jp soono@virology.med.kyushu-u.ac.jp.
Shinji
S
Ohno
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D051338:Cofilin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016679:Genome, Viral; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008459:Measles virus / Q000235:genetics* / Q000378:metabolism; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
D000199:Actins; C495810:CFL1 protein, human; D051338:Cofilin 1; D003598:Cytoskeletal Proteins; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C055859:P protein, Sendai virus; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C028514:actin-modulating proteins; C058314:nucleoprotein, Measles virus