The Varicella-Zoster virus IE4 protein: a conserved member of the herpesviral mRNA export factors family and a potential alternative target in antiherpetic therapies.
During a viral infection, in addition to cellular mRNAs, amounts of viral mRNAs have to be efficiently transported to the cytoplasm for translation. It is now established that herpesviruses encode a conserved gene family whose proteins act as viral mRNA export factors that mediate nucleocytoplasmic transport of viral transcripts and eventually modulate through this mechanism the antiviral response. This conserved family of proteins contains the IE4 protein of the Varicella-Zoster virus (VZV). Here, we compared the functional characteristics of IE4 with those of its herpesviral homologues and proposed a model by which IE4 would be able to recruit the essential TAP/NXF1 receptor to viral transcripts. Moreover, on the basis of their crucial roles in the infectious cycle, these conserved viral factors should be considered as alternative targets in therapeutic approaches. Here, we discussed the possibility of developing antiherpetic agents targeting IE4 or its herpesviral homologues.
Ote
Isabelle
I
Laboratory of Virology and Immunology, GIGA-Research, University of Liège (ULg), B-4000 Liège, Belgium.
Piette
Jacques
J
Sadzot-Delvaux
Catherine
C
D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D024882:Drug Resistance, Viral; D006564:Herpesviridae / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D058990:Molecular Targeted Therapy; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology
D000998:Antiviral Agents; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; C085824:ORF4 protein, Human herpesvirus 3; D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; C446019:pUL69 protein, Human herpesvirus 5