Details:

Alternative Title:
PLoS One
Personal Author:
Dodd, Kimberly A. ; Bird, Brian H. ; Jones, Megan E. B. ; Nichol, Stuart T. ; Spiropoulou, Christina F.
Dodd, Kimberly A. ; Bird, Brian H. ; Jones, Megan E. B. ; Nichol, Stuart T. ; Spiropoulou, Christina F. Less -
Description:
Background

Kyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic fever virus (AHFV) are closely related members of the Flavivirus genus and are important causes of human disease in India and the Arabian Peninsula, respectively. Despite high genetic similarity, the viruses have distinctly different host ranges and ecologies. Human cases of KFDV or AHFV develop a spectrum of disease syndromes ranging from liver pathology to neurologic disease. Case reports suggest KFDV is more commonly associated with hepatic and gastrointestinal manifestations whereas AHFV is more commonly associated with neurologic disease.

Methodology/Principal Findings

Inoculation of three immunocompetent laboratory mouse strains revealed that KFDV was consistently more lethal than AHFV. In subsequent studies utilizing C57BL/6J mice, we demonstrated that KFDV infection was associated with higher viral loads and significantly higher mortality. KFDV-infected mice rapidly developed more severe disease than AHFV-infected mice, as evidenced by significant abnormalities on clinical chemistry panels and more severe pathology in the brain and gastrointestinal tract.

Conclusions/Significance

Infections of C57BL/6J mice with KFDV or AHFV resulted in clinical disease syndromes that closely approximate the diseases seen in human cases. Despite high genetic similarity, there were clear differences in survival, viral kinetics, clinical chemistry data and histology. These results suggest that distinct mouse models for AHFV and KFDV are necessary in order to gain a better understanding of the unique pathogenesis of each virus, as well as to provide platforms for testing promising vaccines and therapeutics.


Subject:
[+]
Animals
Azotemia
Brain
Encephalitis, Tick-Borne
Encephalitis Viruses, Tick-Borne
Female
Gene Expression Regulation
Genome, Viral
Humans
Hypoalbuminemia
Hypoglycemia
Inbreeding
Liver
Lymphopenia
Mice
Morbidity
RNA, Viral
Species Specificity
Time Factors

Source:
PLoS One. 2014; 9(6)
Pubmed ID:
24950196
Pubmed Central ID:
PMC4065072
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:eec9233577ba6d5cc7fb733d8156afe525a299b532aa3bbe2ecb1b542c5aa0aa
File Type:

Supporting Files

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