Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1 (The EMBO J, 2008, 27:3311-3321)

報告日期: 2009/03/10
報告時間: 15:10/16:00
報告學生: 賴曉菁
講評老師: 陳舜華
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980310-1.pdf

Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1

EMBO (2008) 27: 3311-3321

 

Speaker: 賴曉菁

Commentator : 陳舜華 老師

Time: 15:10-16:00, 2009/03/10

Place: Room 602

 

Abstract:

 

    Interferons (IFNs) play an important role in early defense against virus infection and have been used for clinical treatment of virus-associated diseases. The anti-viral effects of IFNs are implemented by IFN-induced proteins, but the functions of these proteins still have not been fully understood. This study found that an IFN-induced protein, P56, binds to human papillomavirus (HPV) E1 protein. The interaction involves the N-terminal tetratricopeptide motif of P56 and the C-terminal region of E1. E1 is an origin-binding protein with helicase and ATPase activities and essential for HPV DNA replication. Type I IFN and double-stranded RNA induce P56 and inhibit HPV DNA replication, and the inhibition can be alleviated by knockdown of P56 expression. In addition, ectopic P56 is sufficient to block HPV DNA replication in both cell-line and cell-free systems, and the blocking effect requires P56’s binding to E1 but not its function to inhibit protein translation. Although cytoplasmic P56 may keep E1 out of the nucleus, P56 in the nucleus can still suppress E1-mediated HPV DNA replication. Further analysis showed P56 inhibits the helicase activity of E1, but not the ATPase activity. This is a novel report that a single IFN-induced protein P56 may exert its anti-viral effect through direct targeting to viral replication machinery. It may also be useful to develop therapeutic strategies of HPV infection.

 

References

1.     Terenzi F., Saikia P., and Sen GC. (2008). Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1. EMBO J 27, 3311-3321.

2.     Sarkar SN., Sen GC. (2004) Novel functions of proteins encoded by viral stress-inducible genes. Pharmacol Ther 103, 243-254.