Multiple proteins differing between laboratory stocks of mammalian orthoreoviruses affect both virus sensitivity to interferon and induction of interferon production during infection

In the course of previous works, it was observed that the virus laboratory stock (T3D(S)) differs in sequence from the virus encoded by the ten plasmids currently in use in many laboratories (T3D(K)), and derived from a different original virus stock. Seven proteins are affected by these sequence differences. In the present study, replication of T3D(K) was shown to be more sensitive to the antiviral effect of interferon. Infection by the T3D(K) virus was also shown to induce the production of higher amount of beta and alpha-interferons compared to T3D(S). Two proteins, the mu 2 and lambda 2 proteins, were found to be responsible for increased sensitivity to it terferon while both mu 2 and lambda 1 are responsible for increased interferon secretion. Altogether this supports the ilea that multiple reovirus proteins are involved in the control of induction of interferon and virus sensitivity to the interferon-induced response. While interrelated, interferon induction and sensitivity can be separated by defined gene combinations. While both mu 2 and lambda 2 were previously suspected of a role in the control of the interferon response, other proteins are also likely involved, as first shown here for lambda 1. This also further stresses that due caution should be exerted when comparing different virus isolates with different genetic background.