Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine

被引：42

作者：

Gladue, D. P.

Holinka, L. G.

Fernandez-Sainz, I. J.

Prarat, M. V.

O'Donell, V. ^{[2
]}

Vepkhvadze, N.

Lu, Z. ^{[3
]}

Rogers, K. ^{[2
]}

Risatti, G. R. ^{[2
]}

Borca, M. V. ^{[1
]}

机构：

[1] ARS, Plum Isl Anim Dis Ctr, USDA, NAA, Greenport, NY 11944 USA

[2] Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA

[3] DHS, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA

来源：

VIROLOGY | 2010年 / 407卷 / 01期

关键词：

Virulence; Pathogenesis; Attenuation; Core protein; Classical swine fever virus; SUMOylation; Vaccines; HEPATITIS-C VIRUS; HOG-CHOLERA VIRUS; HUMAN CYTOMEGALOVIRUS; SUMO-1; MODIFICATION; CELLULAR-TRANSFORMATION; CONJUGATING ENZYME; ENVELOPE PROTEIN; E2; GLYCOPROTEIN; STRAIN BRESCIA; RNA HELICASE;

D O I：

10.1016/j.virol.2010.07.040

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Here we have identified host cell proteins involved with the cellular SUMOylation pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating enzyme that interact with classical swine fever virus (CSFV) Core protein. Five highly conserved lysine residues (K179, K180, K220, K221, and K246) within the CSFV Core were identified as putative SUMOylation sites. Analysis of these interactions showed that K179A, K180A, and K221A substitutions disrupt Core-SUMO-1 binding, while K220A substitution precludes Core-UBC9 binding. In vivo, Core mutant viruses (K179A, K180A, K220A, K221A) and (K220A, K221A) harboring those substitutions were attenuated in swine. These data shows a clear correlation between the disruption of Core protein binding to SUMO-1 and UBC9 and CSFV attenuation. Overall, these data suggest that the interaction of Core with the cellular SUMOylation pathway plays a significant role in the CSFV growth cycle in vivo. Published by Elsevier Inc.

引用

页码：129 / 136

页数：8