Nucleolin is required for an efficient herpes simplex virus type 1 infection.
Productive infection by herpes simplex virus type 1 (HSV-1), which occurs in the host cell nucleus, is accompanied by dramatic modifications of the nuclear architecture, including profound alterations of nucleolar morphology. Here, we show that the three most abundant nucleolar proteins--nucleolin, B23, and fibrillarin--are redistributed out of the nucleoli as a consequence of HSV-1 infection. We show that the amount of nucleolin increases progressively during the course of infection. We demonstrate for the first time that a nucleolar protein, i.e., nucleolin, colocalizes with ICP8 in the viral replication compartments, at the time when viral replication is effective, suggesting an involvement of nucleolin in the HSV-1 DNA replication process. At later times of infection, a granular form of nucleolin localizes to the cytoplasm, in structures that display the characteristic features of aggresomes, indicating that this form of nucleolin is very probably destined for degradation. The delocalization of nucleolin from the nucleoli requires the viral ICP4 protein or a factor(s) whose expression involves ICP4. Using small interfering RNA technology, we show that viral replication requires a high level of nucleolin expression, demonstrating for the first time a direct role for a nucleolar protein in herpes simplex virus biology.
Callé
Aleth
A
Université de Lyon, Lyon F-69003, France.
Ugrinova
Iva
I
Epstein
Alberto L
AL
Bouvet
Philippe
P
Diaz
Jean-Jacques
JJ
Greco
Anna
A
D002458:Cell Fractionation; D002466:Cell Nucleolus / Q000737:chemistry*; D002467:Cell Nucleus / Q000821:virology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D000097796:Nucleolin
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D000097796:Nucleolin; C045462:ICP8 protein, Simplexvirus; C047458:fibrillarin; C048925:herpes simplex virus, type 1 protein ICP4