Reduction in antiviral activity of human interferon-γ in acidic media with reference to structural change

Solution behavior of a novel type 1 interferon, interferon-τ

“…Not all interferons are stable under low pH conditions. In the case of interferon‐γ, there is a reduction in both structural integrity and antiviral activity of the protein when it is formulated in acidic media (<pH 4) 25. Even type 1 interferons have been found to be less stable at low pH.…”

Conformational Stability of Human Interferon‐Gamma on Association with and Dissociation from Liposomes

“…Hoshino et al 17 showed that changes in the environment of the Trp-36 residue result in a decreased antiviral activity, indicating the importance of this region for biological activity. It is imaginable that on interaction with a liposomal bilayer, the dimer dissociates and that hIFN␥ binds in its monomeric form to the surface, with its hydrophobic regions exposed to the hydrophobic interior of the bilayer.…”

“…External factors, such as the pH and ionic strength of the medium, might influence the membrane-protein interactions. [17][18][19] IFN␥ is a molecule of 17 kD that in its bioactive form exists as a homodimer tightly associated by numerous, mostly hydrophobic interhelical interactions. 20 Dissociation of the dimers into monomers is an endothermic process, favored by concentrations of the protein <1 M (17 g/mL) and increasing temperature.…”

Reversibility of acid denaturation of recombinant interferon‐γ

“…7, we assumed the discrepancy between that study and ours is due to perturbation of renaturation by serum proteins present in the sample or medium usually used to dilute protein samples for antiviral assay. Therefore, we tested this possibility by comparing the samples obtained by direct dilution of acid-treated recombinant IFN-y into serum-containing assay medium and by first diluting it into an aqueous buffer and then into the assay medium.…”