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 (less than 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.