Interferon inhibits Sendai virus-induced cell fusion: an effect on cell membrane fluidity.

Abstract

Interferon can affect several cellular functions, in addition to its antiviral activity. We report here that pretreatment of human cells with homologous interferon significantly inhibits cell fusion induced by Sendai virus and that this refractory state is accompanied by a decrease in cell plasma membrane fluidity. Multinucleate cell formation induced by 13-propiolactone-inactivated Sendai virus in human fibroblast cells (a system in which fusion results from an interaction ofthe viral glycoprotein with the cell membrane) was inhibited by more than 90% after addition of human interferon for [18][19][20][21][22][23][24] hr. This inhibition could be neutralized by antiserum to interferon. Furthermore, inhibitor studies with cycloheximide and actinomycin D clearly indicated that synthesis of protein and RNA is necessary to establish the resistant state. To determine whether the inhibition of Sendai virus-induced cell fusion resulted from interferon-induced changes at the cell plasma membrane, experiments were carried out using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene, which is capable of sensing molecular motions in the hydrocarbon core of the bilayer structure. A significant decrease in the membrane fluidity of interferon-treated cells was observed. It is likely, therefore, that the inhibitory effect on Sendai virus-induced cell fusion observed in interferon-treated cells results from an increased rigidity of the target cell membrane.In addition to their potent antiviral action, interferons (IFNs) have various effects on normal cellular functions. It can bind to specific receptors in the plasma membrane of normal and transformed cells and regulate both their motility (1, 2), and their rates of growth and division (3, 4). IFN treatment has also been shown to alter both plasma membrane density and the concentrations of some plasma membrane glycoproteins (5-7). Furthermore, it is known that IFN plays an important role in modulating the immune response of a host to infection (8, 9). It is clear that many of these changes induced by IFN could be mediated by alterations in membrane-associated functions of the treated cell.We showed previously that pretreatment of cells with homologous IFN reduced the number as well as the size of multinucleate cells induced after infection with the type D retrovirus M-PMV (10). These results were consistent with our findings that cell fusion induced by M-PMV and two other type D retroviruses required penetration of the cell by the virus and translation of virus-associated RNA (11,12). Studies from several laboratories had indicated that translation of viral mRNA could be severely inhibited in IFN-treated cells (reviewed in refs. 13 and 14). This inhibition appears to occur via two discrete pathways: the first involves phosphorylation of eukaryotic initiation factor 2 which might prevent the binding oftRNA to 40S ribosomal subunits (15), and the second is through a 2',5' Adependent endonuclease which is activated in IFN-treated cells (16,17).Despite the fact that the...

Interferon treatment inhibits pinocytosis.

“…Inhibition was maximum at 24 h after treatment with 1,000 U of interferon per ml and was dose dependent and reversible with time. Pinocytosis was inhibited when human and chicken embryo cells were treated with homologous, but not heterologous, interferons.In addition to inhibiting viral replication, interferon treatment of cells produces a variety of effects on the plasma membrane (2,3,7,9,12,15) 91:238a, 1981) reported that interferon treatment of thioglycollate-elicited mouse peritoneal macrophages caused a marked change in the distribution of microtubules and 10-nm filaments in a major fraction of the cells; this alteration was correlated with an inhibition of pinocytosis. The results reported here describe some details of the inhibition of pinocytosis in cells treated with interferon.…”

Armand-Frappier Outstanding Student Award — The emerging role of 25-hydroxycholesterol in innate immunity

“…Both studies confirmed broad antiviral activity of 25HC in vitro against different classes of lipid-enveloped RNA and DNA viruses. This was subsequently reaffirmed by several independent studies (Arita et al 2013;Chen et al 2014;Mboko et al 2014), and the antiviral activity was additionally extended to nonenveloped viruses (Civra et al 2014). Table 1 summarizes the viruses whose susceptibility to 25HC's antiviral effects has been validated.…”

The influence of porcine recombinant interferon- 1 on pseudorabies virus infection of porcine nasal mucosa in vitro

“…IFN inhibits the production of viral glycoproteins, thus affecting the membrane-associated steps of viral replication (Chatterjee et al, 1985). Alternatively, IFN may change the fluidity of membranes and thereby disrupt viral morphogenesis (Chatterjee et al, 1982;Pfeffer et al, 1981 ;Wang et al, 1981).…”