FIGURE 5.

SPIKENET (SPK) diminishes MHV-1-induced pathological changes in lung, liver, kidney, heart and brain. Representative histological images of hematoxylin and eosin (H&E) stained lung, liver, kidney, heart and brain tissue sections of a normal mouse (A,D,G,J,M,P) and an infected mouse at day 7 (B,E,H,K,N,Q). “MHV-1-infected mice lungs showed arterial endothelial swelling, inflammation/granular degeneration of cells and migration of leukocytes into lung (arrow). Peribronchiolar interstitial infiltration, bronchiole epithelial cell necrosis and necrotic cell debris within alveolar lumens, alveolar exudation, infiltration, hyaline membrane formation and alveolar hemorrhage with red blood cells within the alveolar space and interstitial edema were also observed in MHV-1-infected mice (B). MHV-1-infected mice at day 7 showed hepatocyte degeneration, severe periportal hepatocellular necrosis with pyknotic nuclei, severe hepatic congestion (arrowheads), ballooned hepatocytes (arrow), vacuolation and the presence of piecemeal necrosis, as well as hemorrhagic changes and hemorrhagic changes when compared to uninfected mice (E). Kidney from an MHV-1 infected mouse showed proximal and distal tubular necrosis (arrowheads), hemorrhage in the interstitial tissue (arrow), and vacuolation of renal tubules (H). MHV-1 infected mouse heart showed severe interstitial edema (arrows), vascular congestion and dilation (arrowheads), and red blood cell extravasation into the interstitium (K). Congested blood vessels (arrowhead), pericellular halos (short arrow), pyknotic nuclei amid associated vacuolation of the neuropil (long arrows), perivascular cavitation suggestive of edema, vacuolation of neuropils, darkly stained nuclei, and acute eosinophilic necrosis were observed in MHV- 1-treated mice (N,Q), as compared to untreated mice” (Paidas et al., 2021). MHV-1 inoculated mice treated with 5 mg/kg SPIKENET (SPK) ameliorated all of these changes (C,F,I,L,O,R) (H&E original magnification is ×400 for all images).