Cell surface receptor-mediated internalization of interferon: its relation to the antiviral activity of interferon

The binding of [3 H]leucine-labelled pure human interferon c ~ from Namalwa cells to human FL and Daudi cells was studied, and evidence obtained to indicate receptor-mediated internalization of interferon. Cell surface-bound and internalized interferons were quantified separately as trypsin-released and unreleased radioactivities, respectively. At 37 °C, surface-bound interferon reached amaximum after 1 h and then decreased, while internalized interferon reached a maximum after 2 h. At 21 °C, in contrast, surface-bound interferon reached a maximum after 2 h and did not decrease thereafter; no internalization was observed. The same was true at 37 °C in the presence of NaF, indicating dependence of internalization on temperature and energy. In control cultures at 37 °C, internalized interferon, after reaching amaximum, decreased after prolonged incubation, and concomitantly acid-soluble radioactivity appeared in the culture medium. The decrease in internalized interferon and the emergence of degraded interferon were inhibited by the lysosomotropic agents, ammonium chloride and chloroquine. The fate of labelled interferon, bound to the cell surface of FL cells at 21 °C, was studied at 37 °C, and the results indicated that trypsin-unreleased interfero