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J. Virol. doi:10.1128/JVI.01074-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. 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 1 interferon antagonist

Departments of Pathology, Pathology, Microbiology and Immunology, Centers for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA 77550-0609

^* To whom correspondence should be addressed. Email: cjpeters{at}utmb.edu.

	Abstract

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 non-lethal 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 LD₅₀'s for each PTV genotype [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 / IFN in vivo and in vitro and inhibits the activation of the IFN- promoter. Expression of the PTV Adames NSs protein, encoded by the S RNA segment, inhibited the virus-mediated induction of an IFN- 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 1 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.

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