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Journal of Virology, January 2007, p. 884-892, Vol. 81, No. 2
0022-538X/07/$08.00+0 doi:10.1128/JVI.01074-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
The S Segment of Punta Toro Virus (Bunyaviridae, Phlebovirus) Is a Major Determinant of Lethality in the Syrian Hamster and Codes for a Type I Interferon Antagonist
Lucy A. Perrone,1,
Krishna Narayanan,2
Melissa Worthy,2,
and
C. J. Peters1,2*
Departments of Pathology,1 Microbiology and Immunology, Centers for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 77550-06092
Received 24 May 2006/ Accepted 5 October 2006
Two
strains of Punta Toro virus (PTV), isolated from febrile humans in
Panama, cause a differential pathogenesis in Syrian hamsters, which
could be a useful model for understanding the virulence characteristics
and differential outcomes in other phleboviral infections such as Rift
Valley fever virus. Genetic reassortants produced between the lethal
Adames (A/A/A) and nonlethal Balliet (B/B/B) strains were used in this
study to investigate viral genetic determinants for pathogenesis and
lethality in the hamster model. The S segment was revealed to be a
critical genome segment, determining lethality with log10
50% lethal doses for each PTV genotype as follows (L/M/S convention):
A/A/A, <0.7; B/A/A, <0.7; A/B/A, 1.5; B/B/A, 2.2;
B/A/B, 4.7; A/B/B, >4.7; A/A/B, >4.7; B/B/B,
>4.7. In addition, the Adames strain inhibits the induction of
alpha/beta interferon (IFN-
/ß) in vivo and in vitro
and inhibits the activation of the IFN-ß promoter. Expression
of the PTV Adames NSs protein, encoded by the S RNA segment, inhibited
the virus-mediated induction of an IFN-ß promoter-driven
reporter gene, suggesting that PTV NSs functions as a type I IFN
antagonist. Taken together, these data indicate a mechanism of
pathogenesis in which the suppression of the type I IFN response early
during PTV infection leads to early and uncontrolled viral replication
and, ultimately, hamster death. This study contributes to our
understanding of Phlebovirus pathogenesis and identifies
potential targets for immune modulation to increase host
survival.
* Corresponding author. Mailing address: 301 University Blvd., Galveston, TX 77550-0609. Phone: (409) 772-0090. Fax: (409) 747-0602. E-mail: cjpeters{at}utmb.edu.
Published ahead of print on 18 October 2006.
Present
address: Influenza Division, Immunology and Pathogenesis Branch, MS
G-16, CCID, NCIRD, Centers for Disease Control and Prevention, 1600
Clifton Road, N.E., Atlanta, GA 30033.
Present
address: Texas A&M University, College of Veterinary Medicine,
Department of Veterinary Pathobiology; MS 4467, College Station, TX
77843.
Journal of Virology, January 2007, p. 884-892, Vol. 81, No. 2
0022-538X/07/$08.00+0 doi:10.1128/JVI.01074-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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