Histopathological changes in the myocardium of animals infected with CVB-H3 (FP41, FP44, and FP46) and CVB3-MCH (FP47).

<p>FP41 (A) exhibiting prominent cytoplasmic vacuolization indicative of myocytolysis (400X; H&E stain). FP44 (B) revealing focal, predominantly lymphocytic, mononuclear inflammatory infiltrate with associated myocyte injury consistent with myocarditis (400X; H&E stain). FP46 (C) showing hypereosinophilic, hypercontracted myofibrils indicative of contraction band necrosis of cardiac myocytes (right lower corner) (400X; H&E stain). FP47 (D) demonstrating focal mononuclear inflammatory infiltrate without associated myocardial injury (400X; H&E stain).</p

Plasma cytokine concentrations following intravenous inoculation with CVB3.

<p>Concentrations of single cytokines IFN-g (panel A), TNF-a (Panel B), and IL-6 (panel C) are demonstrated. Mean cytokine concentrations for the two animals receiving high dose (10⁷ pfu) CVB-H3 by i.v. (▪) or the single animal infected by enteral infection (<b>○</b>) are shown. Mean cytokine concentration +/− SEM for animals receiving low dose (10⁶ pfu) CVB-H3 (▴) or CVB-MCH (Δ) by i.v. are shown</p

Coxsackievirus viral load (plasma viral RNA copies/ml) (dashed lines) and neutralizing antibody titers (reciprocal of dilution) (solid lines) after intravenous infection of two cynomolgus monkeys: FP42 (closed figures) and FP49 (open figures).

<p>Coxsackievirus viral load (plasma viral RNA copies/ml) (dashed lines) and neutralizing antibody titers (reciprocal of dilution) (solid lines) after intravenous infection of two cynomolgus monkeys: FP42 (closed figures) and FP49 (open figures).</p

Immunohistochemistry of myocardial tissue.

<p>Upper left panel: H&E stain. Antibody specificity used for immunoperoxidase staining is listed below remaining panels. (All sections at 400X)</p

Biomarkers measured in animals inoculated with low dose (10⁶ pfu) CVB-H3 or CVB-MCH.

<p>Serum, unfractionated LDH (▪), total CPK (•), and ALT (□) are represented as mean +/− SEM for all 6 animals at each timepoint.</p

Summary of Animals and Virologic Studies.

<p>1. Limit of detection approximately 10,000 copies/ml. “<b>-</b>“  =  not detected.</p><p>2. Viral RNA detected in tissue from chamber designated. LA =  left atrium, RA  = right atrium, LV  =  left ventricle, RV  =  right ventricle.</p><p>3. Only RV, LV, and RA tissue available from this animal.</p><p>4. See text for description.</p

Postmortem histopathologic findings (hematoxylin-eosin (H&E) stain) of two cynomolgus monkeys injected with 10⁷ pfu of CVB3-H3.

<p>Myocardium from both FP42 (A (200X)) and FP49 (D (200X)) showed evidence of viral myocarditis, consisting of focal predominantly lymphocytic mononuclear inflammatory infiltrates with myocyte injury. In addition, representative sections of the liver from both animals exhibited changes of mild viral hepatitis including focal mononuclear inflammatory infiltrates within the hepatic lobules (B (FP42)) and portal tracts with associated interface hepatitis (E (FP49)). The central nervous system exhibited perivascular lymphocytic infiltrates within the leptomeninges (C (FP42)) and intracerebral blood vessels (F (FP49)) with microglial proliferation and nodules (not shown). These changes are indicative of viral meningitis and encephalitis (meningoencephalitis).</p