Extracellular matrix remodelling after coxsackievirus B3-induced murine myocarditis

Abstract

Weanling inbred Balb/c mice were intraperitoneally inoculated with a myocarditic variant of coxsackievirus B3. At days 1, 2, 4, 6, 8, 10, 14, 24 and 30 post-infection (p.i.), myocardial tissue was harvested for viral infectivity titrations and histological studies, including routine techniques (haematoxylin-eosin, Masson trichrome and von Kossa) and specialized procedures (silver impregnation for reticulin, picrosirius red stain for collagen and immunoperoxidase labelling for laminin). Virus was isolated as from day 2, reached maximal infectivity at days 6-8 and decreased gradually to become undetectable by day 14. Early histological findings during the 1st week consisted mainly of scattered foci of necrotic myocytes showing calcium deposits; slight mononuclear cell infiltration and fragmentation of both reticulin fibres and pericellular laminin were also present. From the 2nd up to 4th week p.i., inflammatory reaction abated concomitantly with the gradual development of fibrosis, as evidenced by reticulin fibre thickening, irregular laminin distribution and collagen fibre increase. Our results suggest that viral-induced necrosis is able to trigger marked extracellular matrix remodelling even in the case of minimal inflammation.