Cytokine storms and pyroptosis are primarily responsible for the rapid death of mice infected with pseudorabies virus

<p><span>Pseudorabies virus</span><b><span> (</span></b><span>P</span><span>R</span><span>V) , </span><span>the</span> <span>causative</span> <span>agent</span> <span>of</span> <span>Aujeszky's</span> <span>disease</span><span> (AD), is one of the most harmful pathogens to </span><span>the </span><span>pig </span><span>indus</span><span>t</span><span>ry</span><span>. </span><span>P</span><span>R</span><span>V </span><span>can</span><span> infect and kill a variety of mammals. </span><span>N</span><span>evertheless, the underlying p</span><span>athogenesis</span><span> related to PRV </span><span>is </span><span>still unclear</span><span>.</span><span> Th</span><span>is </span><span>study </span><span>aim</span><span>s</span><span> to </span><span>investigate</span><span> the </span><span>p</span><span>athogenesis induced by </span><span>PRV</span><span> in a mouse model. </span><span>The mice infected with </span><span>the </span><span>PRV-HLJ </span><span>str</span><span>a</span><span>in</span> <span>were </span><span>developed s</span><span>evere clinical manifestations </span><span>at</span> <span>36 hour post</span><span>-</span><span>infection</span> <span>(hpi)</span><span>, and </span><span>m</span><span>ortality occurred within </span><span>48</span><span>-</span><span>72</span><span> hpi</span><span>.</span><span> H</span><span>ematoxylin</span><span>-</span><span>eosin staining </span><span>and q</span><span>RT</span><span>-PCR</span><span> method</span><span>s</span><span> w</span><span>ere</span><span> used to detect the pathological damage </span><span>and </span><span>expression of cytokines </span><span>related to </span><span>immune</span><span> reaction</span><span> in </span><span>brain tissue</span><span>, respe</span><span>c</span><span>tively</span><span>.</span><span> T</span><span>he cytokine sto</span><span>r</span><span>ms caused by </span><span>IFN-α</span><span>, </span><span>IFN-β</span><span>, </span><span>TNF-α</span><span>, </span><span>IL-1β, IL-6</span><span> and IL-1</span><span>8 </span><span>were</span> <span>related to the histopathol</span><span>o</span><span>gical changes induced by PRV.</span><span> This pattern </span><span>of </span><span>cytokine secretion depicts an image of</span><span> typical cytokine storm</span><span>s</span><span>, characterized by dysregulated secretion of pro-inflammatory cytokines and </span><span>imbalanced</span><span> pro-inflammatory and anti-inflammatory responses</span><span>. </span><span>I</span><span>n addition, </span><span>the pyroptosi</span><span>s</span><span> pathway was </span><span>also activated by</span> <span>PRV </span><span>by</span><span> elevating the </span><span>expression levels of nod-like receptor protein 3, caspase-1, gasd</span><span>er</span><span>min-D and interleukin-1β</span><span>/18. </span><span>These findings </span><span>provide a way for </span><span>further understanding the molecular basis </span><span>in PRV</span><span> pathogenesis.</span></p>