Isolation and characterization of a soluble form of the LDL receptor, an interferon-induced antiviral protein.

Abstract

Interferons (IFNs) act by inducing several intracellular antiviral proteins. We report here that IFNs also induce an extracellular soluble protein that inhibits vesicular stomatitis virus (VSV) infection. This protein accounts for 25%-50% of the total antiviral activity elicited by IFN. The antiviral protein was purified to homogeneity from culture supernatants of IFN-treated cells by several chromatographic steps, to give a single 28-kDa active polypeptide. Upon sequencing, this novel protein corresponded to the N-terminal ligand-binding domain of the human 160-kDa low-density lipoprotein receptor (LDLR). In addition, we find that IFN induces the cell surface LDLR and this phenomenon may explain previous reports on reduction of serum cholesterol in IFN-treated patients. Viruses produce soluble cytokine receptors that inhibit their respective cytokines, thereby assisting virus infection. It appears now that host cells employ similar molecules for the opposite role of controlling virus infections.