Interaction between Core protein of classical swine fever virus with cellular IQGAP1 protein appears essential for virulence in swine.
Here we show that IQGAP1, a cellular protein that plays a pivotal role as a regulator of the cytoskeleton interacts with Classical Swine Fever Virus (CSFV) Core protein. Sequence analyses identified residues within CSFV Core protein (designated as areas I, II, III and IV) that maintain homology to regions within the matrix protein of Moloney Murine Leukemia Virus (MMLV) that mediate binding to IQGAP1 [EMBO J, 2006 25:2155]. Alanine-substitution within Core regions I, II, III and IV identified residues that specifically mediate the Core-IQGAP1 interaction. Recombinant CSFV viruses harboring alanine substitutions at residues (207)ATI(209) (I), (210)VVE(212) (II), (213)GVK(215) (III), or (232)GLYHN(236) (IV) have defective growth in primary swine macrophage cultures. In vivo, substitutions of residues in areas I and III yielded viruses that were completely attenuated in swine. These data shows that the interaction of Core with an integral component of cytoskeletal regulation plays a role in the CSFV cycle.
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY 11944, USA. douglas.gladue@ars.usda.gov
D P
DP
Gladue
L G
LG
Holinka
I J
IJ
Fernandez-Sainz
M V
MV
Prarat
V
V
O'Donnell
N G
NG
Vepkhvadze
Z
Z
Lu
G R
GR
Risatti
M V
MV
Borca
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D006691:Classical Swine Fever / Q000473:pathology / Q000821:virology; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000821:virology; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D014758:Viral Core Proteins; D020703:ras GTPase-Activating Proteins