The Relationship Between Interferon and Virus Virulence in Influenza Virus Infections of the Mouse

Abstract

THERE have been many attempts to explain the virulence of viruses on the basis of their sensitivity to interferon or their ability to induce interferon in infected cells. Enders (1962) and De Maeyer and Enders (1965) observed that an attenuated strain of measles virus induced larger amounts of interferon than did a virulent strain, but considered that the poorer growth of the attenuated strain was probably not due to the increased production of interferon. Ruiz-Gomez and Isaacs (1963a) studied a number of different viruses and reported that the more virulent ones induced the least amounts of interferon. Similar results were obtained for strains of Semliki Forest, measles and Japanese encephalitis viruses (Finter, 1964;Mirchamsy and Rapp, 1969;Rokutanda, 1969). Vilikk (1964), however, found that the amount of interferon produced in mice infected with Sindbis virus was directly related to virus multiplication and he concluded that interferon formation was more probably a secondary response to, rather than a determining factor in, virus replication. The results obtained by different workers who have attempted to relate virulence to the sensitivity of the viruses to inhibition by interferon have also been contradictory. RuizGomez and Isaacs (1963b), in studies of arboviruses, myxoviruses and poxviruses, found that, with some exceptions, sensitivity to interferon was inversely related to virulence. Similar results have been reported for strains of foot-and-mouth disease virus (Sellers, 1963) and Semliki Forest virus (Finter, 1964). On the other hand, Campbell and Colter found that three variants of Mengo virus which possessed different degrees of virulence for mice had the same sensitivity to interferon; Rokutanda had similar findings with strains of Japanese encephalitis virus.The present study compares the virulence of influenza viruses for mice with the amount of interferon induced by them in the lungs of infected mice and with their in-vitro sensitivity to inhibition by interferon. The findings do not agree with the theory that virus virulence is determined by the properties of poor induction of interferon and low sensitivity to the inhibitory action of interferon, but indicate rather that the amount of interferon induced is determined by the degree of virus replication. MATERIALS AND METHODS Virus strainsThe Ao/WSN (HON1) parent strain of influenza virus and a number of temperaturesensitive (ts) mutants derived from it by 5-fluorouracil treatment were obtained, as lyophilised

Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus.

“…:~ Probability P as indicated in Table I. (17). The susceptibility of immature Mx bearers may be related to their inability to make adequate amounts of interferon, rather than to their inability to respond to it.…”

Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone

“…Taken together, these data indicate that the serum and lung inhibitors stimulated by 9-MS were interferon. DISCUSSION Influenza virus has generally been regarded as more sensitive to the action of interferon (17,20) than herpes simplex and other viruses (3). It has generally been reported that the prophylactic administration of such interferon inducers as polyinosinic:polycytidylic acid (injected i.p.…”

Type I IFN Receptor Signals Directly Stimulate Local B Cells Early following Influenza Virus Infection

“…Influenza infection causes rapid induction of type I IFN secretion in the respiratory tract (2,3). IFN is a well-known family of antiviral cytokines that can be secreted by virtually all host cells (11).…”