The E2 glycoprotein of classical swine fever virus is a virulence determinant in swine.
To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.
Risatti
G R
GR
Plum Island Animal Disease Center, USDA/ARS/NAA, P.O. Box 848, Greenport, NY 11944-0848, USA.
Borca
M V
MV
Kutish
G F
GF
Lu
Z
Z
Holinka
L G
LG
French
R A
RA
Tulman
E R
ER
Rock
D L
DL
D000818:Animals; D001483:Base Sequence; D018929:Cell Culture Techniques; D006691:Classical Swine Fever / Q000473:pathology / Q000821:virology; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000821:virology; D011995:Recombination, Genetic; D013552:Swine; D014759:Viral Envelope Proteins / Q000502:physiology*; D014766:Viremia; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology*
D014759:Viral Envelope Proteins; D037521:Virulence Factors; C087086:glycoprotein E2, classical swine fever virus
Dtsch Tierarztl Wochenschr. 1999 Sep;106(9):394-7
10547932
Genome Res. 1999 Sep;9(9):868-77
10508846
J Virol. 2000 Apr;74(7):2973-80
10708411
Vet Microbiol. 2000 Jun 12;74(4):293-308
10831853
J Virol. 2000 Oct;74(20):9553-61
11000226
Vaccine. 2000 Oct 15;19(4-5):447-59
11027808
Virus Genes. 2001;23(1):63-8
11556403
J Virol. 2001 Oct;75(20):9585-95
11559790
Vaccine. 2002 Feb 22;20(11-12):1544-56
11858861
J Virol. 2002 Aug;76(16):8494-503
12134054
J Clin Microbiol. 2003 Jan;41(1):500-5
12517907
Virology. 2003 Mar 15;307(2):255-65
12667795
J Gen Virol. 2003 May;84(Pt 5):1269-74
12692293
Vaccine. 2004 Jan 2;22(3-4):317-28
14670312
J Virol. 2004 Aug;78(16):8812-23
15280489
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
271968
Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95
6546423
Dtsch Tierarztl Wochenschr. 1990 Feb;97(2):77-9
2311534
J Virol. 1990 Aug;64(8):3563-9
2370675
J Virol. 1991 May;65(5):2761-5
1850051
J Virol. 1991 Sep;65(9):4705-12
1870198
Vet Microbiol. 1991 Oct;29(2):101-8
1660637
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2002-6
1549558
J Virol. 1993 Sep;67(9):5435-42
8350404
Biochemistry. 1994 Mar 15;33(10):3038-49
8130217
J Virol. 1994 Jun;68(6):3934-42
7514680
J Virol. 1995 Oct;69(10):6479-86
7666549
J Clin Microbiol. 1996 Sep;34(9):2280-6
8862599
J Virol. 1996 Dec;70(12):8865-71
8971015
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694
J Gen Virol. 1997 Nov;78 ( Pt 11):2779-87
9367363
Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
9396791
J Virol. 1998 Jan;72(1):151-7
9420210
J Virol. 1998 Sep;72(9):7681-4
9696875
J Gen Virol. 1999 May;80 ( Pt 5):1157-65
10355762
J Mol Biol. 1999 Sep 17;292(2):195-202
10493868
J Virol. 1999 Dec;73(12):10224-35
10559339