Induction of the 2-5A System by Interferon and Transmissible Gastroenteritis Virus

Abstract

Interferon (IFN) treatment increased the level of 2'',5''-oligoadenylate (2-5A) synthetase and inhibited replication of transmissible gastroenteritis virus (TGEV) in cultured swine testicular cells. Despite a minimal increase in TGEV titer in IFN-treated swine testicular cells, there was rapid cellular destruction. IFN-treated swine testicular cells had detectable levels of 2-5A (3.6 nM 6 h post-infection) after infection with 30 pfu TGEV/cell. Infection of neonatal pigs with a virulent strain of TGEV caused a significant increase in serum IFN and enterocyte 2-5A synthetase activity, as compared to control pigs. The level of enterocyte 2-5A synthetase in TGEV-infected pigs was increased 25-fold before viral-induced damage of the intestine consistently was present. 2-5A was not detected in enterocytes of either TGEV-infected or control pigs (< 0.5 nM). Preparations of enterocytes contained two subpopulations of cells, one of which does not support replication of the virus. The considerable dilution of TGEV-infected cells (villous enterocytes) with uninfected cells (crypt cells) may be responsible for our inability to detect 2-5A in enterocytes from TGEV-infected pigs. These results indicate that the 2-5A system in porcine enterocytes and cultured testicular cells is modulated by TGEV infection and/or interaction with IFN.