Mouse cytomegalovirus. Necrosis of infected and morphologically normal submaxillary gland acinar cells during termination of chronic infection.

The ultrastructural lesions in the submaxillary glands of C(3)H mice chronically infected with the murine cytomegalovirus are reported. Virus was synthesized in the nucleus of acinar glandular cells. After passage into the cytoplasm, virus was located in large vesicles which were derived from the Golgi apparatus. These vesicles, which were periodic acid-Schiff positive, migrated to the apex of the cell and released virus into the acinar lumen or canaliculi. Eventually, lymphocytes infiltrated the interstitium and surrounded the basal lamina of acini which contained infected cells. In acini encompassed by lymphocytes, both infected cells and morphologically normal acinar cells simultaneously degenerated, producing a small focus of necrosis. Physical contact between lymphocytes and necrotic cells did not occur for an intact basal lamina was always found interposed between them. Degeneration of infected cells coincided with a decrease in virus titer in the salivary glands. Degeneration of infected and normal acinar cells also occurred in DBA 2 mice which lack the fifth component of complement. In mice conditioned with cortisone to suppress inflammation, neither infected nor normal acinar cells degenerated. We concluded from the electron microscope observations that lymphocytes terminate chronic MCMV infection, that MCMV infection of acinar epithelium is not cytolytic and that normal cells also undergo necrosis during termination of chronic MCMV infection. It is postulated that lymphocytes in responding to infection release a cytotoxic substance which diffuses into the acini and causes indiscriminate necrosis of acinar cells.