1918 H1N1 influenza virus replicates and induces pro-inflammatory cytokine responses in extra-respiratory tissues of ferrets

Emmie de Wit,etc.,al. 1918 H1N1 influenza virus replicates and induces pro-inflammatory cytokine responses in extra-respiratory tissues of ferrets. J Infect Dis 10 Jan 2018
submited by kickingbird at Jan, 13, 2018 15:1 PM from J Infect Dis 10 Jan 2018

Background

The 1918 Spanish H1N1 influenza pandemic was the most severe recorded influenza pandemic with an estimated 20-50 million deaths worldwide. Even though it is known that influenza viruses can cause extra-respiratory tract complications—which are often severe or even fatal— the potential contribution of extra-respiratory tissues to the pathogenesis of 1918 H1N1 virus infection has not been studied comprehensively.

Methods

Here, we performed a time course study in ferrets inoculated intranasally with 1918 H1N1 virus, with special emphasis on the involvement of extra-respiratory tissues. Respiratory and extra-respiratory tissues were collected after inoculation for virological, histological and immunological analysis.

Results

Infectious virus was detected at high titers in respiratory tissues, and—at lower titers—in most extra-respiratory tissues. Evidence for active virus replication, as indicated by the detection of nucleoprotein by immunohistochemistry, was observed in the respiratory tract, peripheral and central nervous system, and liver. Pro-inflammatory cytokines were upregulated in respiratory tissues, olfactory bulb, spinal cord, liver, heart and pancreas.

Conclusions

1918 H1N1 virus spread to, and induced cytokine responses in tissues outside the respiratory tract, which likely contributed to the severity of infection. Moreover, our data support the suggested link between 1918 H1N1 infection and CNS disease.