In:
Journal of Virology, American Society for Microbiology, Vol. 81, No. 2 ( 2007-01-15), p. 884-892
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 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 log 10 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-α/β) in vivo and in vitro and inhibits the activation of the IFN-β promoter. Expression
of the PTV Adames NSs protein, encoded by the S RNA segment, inhibited the virus-mediated induction of an IFN-β 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.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.01074-06
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2007
detail.hit.zdb_id:
1495529-5
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