Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity

被引：80

作者：

Bergeron, Eric ^{[1
]}

Vincent, Martin J. ^{[1
]}

Nichol, Stuart T. ^{[1
]}

机构：

[1] Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30329 USA

来源：

JOURNAL OF VIROLOGY | 2007年 / 81卷 / 23期

关键词：

D O I：

10.1128/JVI.01647-07

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease. The CCHFV medium RNA encodes a polyprotein which is proteolytically processed to yield the glycoprotein precursors PreGn and PreGc, followed by structural glycoproteins Gn and Gc. Subtilisin kexin isozyme-1/site-1 protease (SKI-1/SIP) plays a central role in Gn processing. Here we show that CCHFV-infected cells deficient in SKI-1/SIP produce no infectious virus, although PreGn and PreGc accumulated normally in the Golgi apparatus, the site of virus assembly. Only nucleoprotein-containing particles which lacked virus glycoproteins (Gn/Ge or PreGn/PreGc) were secreted. Complementation of SKI-1/SlP-deficient cells with a SKI-1/SIP expression vector restored release of infectious virus (> 10(6) PFU/ml), confirming that SKI-1/SIP processing is required for incorporation of viral glycoproteins. SKI-1/SIP may represent a promising antiviral target.

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页码：13271 / 13276

页数：6

相关论文

共 29 条

[11] EXPRESSION AND SUBCELLULAR LOCATION OF THE NSM PROTEIN OF TOMATO SPOTTED WILT VIRUS (TSWV), A PUTATIVE VIRAL MOVEMENT PROTEIN [J].

KORMELINK, R ;

STORMS, M ;

VANLENT, J ;

PETERS, D ;

GOLDBACH, R .

VIROLOGY, 1994, 200 (01) :56-65

[12] Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions [J].

Kunz, S ;

Edelmann, KH ;

de la Torre, JC ;

Gorney, R ;

Oldstone, MBA .

VIROLOGY, 2003, 314 (01) :168-178

[13] The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P [J].

Lenz, O ;

ter Meulen, J ;

Klenk, HD ;

Seidah, NG ;

Garten, W .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (22) :12701-12705

[14] The Hantaan virus glycoprotein precursor is cleaved at the conserved pentapeptide WAASA [J].

Löber, C ;

Anheier, B ;

Lindow, S ;

Klenk, HD ;

Feldmann, H .

VIROLOGY, 2001, 289 (02) :224-229

[15] EXPRESSION OF THE BUNYAMWERA VIRUS-M GENOME SEGMENT AND INTRACELLULAR-LOCALIZATION OF NSM [J].

NAKITARE, GW ;

ELLIOTT, RM .

VIROLOGY, 1993, 195 (02) :511-520

[16] Reverse genetics demonstrates that proteolytic processing of the Ebola virus glycoprotein is not essential for replication in cell culture [J].

Neumann, G ;

Feldmann, H ;

Watanabe, S ;

Lukashevich, I ;

Kawaoka, Y .

JOURNAL OF VIROLOGY, 2002, 76 (01) :406-410

[17] Proteolytic processing of the Ebola virus glycoprotein is not critical for Ebola virus replication in nonhuman primates [J].

Neumann, Gabriele ;

Geisbert, Thomas W. ;

Ebihara, Hideki ;

Geisbert, Joan B. ;

Daddario-DiCaprio, Kathleen M. ;

Feldmann, Heinz ;

Kawaoka, Yoshihiro .

JOURNAL OF VIROLOGY, 2007, 81 (06) :2995-2998

[18] Luman, the cellular counterpart of herpes simplex virus VP16, is processed by regulated intramembrane proteolysis [J].

Raggo, C ;

Rapin, N ;

Stirling, J ;

Gobeil, P ;

Smith-Windsor, E ;

O'Hare, P ;

Misra, V .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (16) :5639-5649

[19] Isolation of cholesterol-requiring mutant Chinese hamster ovary cells with defects in cleavage of sterol regulatory element-binding proteins at site 1 [J].

Rawson, RB ;

Cheng, D ;

Brown, MS ;

Goldstein, JL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) :28261-28269

[20] Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells [J].

Sakai, J ;

Rawson, RB ;

Espenshade, PJ ;

Cheng, D ;

Seegmiller, AC ;

Goldstein, JL ;

Brown, MS .

MOLECULAR CELL, 1998, 2 (04) :505-514