The Role of Viral Glycoproteins in Mumps‐Virus‐dependent Lymphocyte‐mediated Cytotoxicity in Vitro

Abstract

Human peripheral blood lymphocytes (PBL) from healthy donors express enhanced natural cytotoxicity to target cells after a brief exposure 10 mumps virus in vitro, We describe here experiments aiming at elucidating the mechanism of this virus-dependant cytotoxicity. Treatment with proteolytic enzymes resulted in virus particles depleted of one or both kinds of their glycoprotein spikes. Removal of both of these components from the virion abrogated their ability to enhance cytotoxicity. This virus-dependent cytotoxicity was significantly but not completed reduced when one of the spike glycoproteins (gp 75, HANA) was removed selectively. Similarly, nucleic-acid-free preparations of the spikes, obtained by detergent treatment of mumps virions, also dialed enhanced cytotoxicity. However, the activity of these preparations was lower than that of untreated virions Further evidence for the importance of II AN A was provided by the use of F(ab′)₂ fragments of anti-HANA-specific rabbit antibodies. When these fragments were allowed to react with virus before addition of the virus to PBL. no augmentation of cytolysis was observed. Antibody fragments specific for the other spike protein (gp 61, F) failed to inhibit the virus-dependent enhancement of PBL-mediated cytotoxicity. However, anti-HANA and anti-F blocked this reaction when added directly to the mixture of virus-treated PBL and target cells. The results are compatible with the hypothesis that virus-dependent cytotoxicity requires HANA for anchoring the virus to PBL receptors (and perhaps to bring effector and target cells into closer contact), whereas F may be involved in subsequent events increasing effector cell function.