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. 2010 Aug 12;5(8):e12099.
doi: 10.1371/journal.pone.0012099.

Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus

Xue Wang  1 , Jiangqin Zhao, Shixing Tang, Zhiping Ye, Indira Hewlett
Affiliations

Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus

Xue Wang et al. PLoS One. .

Abstract

Avian H5N1 influenza viruses cause severe disease and high mortality in infected humans. However, tissue tropism and underlying pathogenesis of H5N1 virus infection in humans needs further investigation. The objective of this work was to study viremia, tissue tropism and disease pathogenesis of H5N1 virus infection in the susceptible ferret animal model. To evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the H5N1 strain A/VN/1203/04 to assess clinical signs after infection and virus load in lung, brain, ileum, nasal turbinate, nasal wash, and blood. We observed that H5N1 infection in ferrets is characterized by high virus load in the brain and and low levels in the ileum using real-time PCR. In addition, viral RNA was frequently detected in blood one or two days before death and associated with symptoms of diarrhea. Our observations further substantiate pathogenicity of H5N1 and further indicate that viremia may be a bio-marker for fatal outcomes in H5N1 infection.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Clinical signs of infection with H5N1 virus A/VN/1203/04 in ferrets.
(A) Changes in body temperatures of infected ferrets. Ferrets were inoculated with either 1 FLD50 or 10 FLD50 of the viruses, and body temperatures were monitored daily by the use of subcutaneous implantable temperature transponders for 11 days postinfection. Each data point represents the mean value ± SD for the surviving ferret(s). Note: only one animal remained alive in the 10 FLD50 group (one value) on Day 9 postinfection. (B). Changes in weights of ferrets infected with the viruses. The weights of ferrets were measured daily. The loss or gain of weight was calculated for each ferret as the percent change in the initial mean starting weight on day 0. Values are the averages ± SD for the ferret(s) alive for each group. (C) Virus titer in nasal wash with FLD50 assay. Nasal washes were performed on Day 2, Day 4, and Day 6 postinfection in selection of ferrets in both groups using FLD50 assay.
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