In vitro generation of human cytotoxic lymphocytes by virus. Viral glycoproteins induce nonspecific cell-mediated cytotoxicity without release of interferon.

Abstract

Purified hemagglutinin and fusion glycoproteins of measles virus, in soluble form or inserted in artificial membranes, bind to human peripheral blood lymphocytes and induce cell-mediated cytotoxicity (CMC) in a dose-response fashion. Autologous and heterologous noninfected target cells are lysed in vitro. The expression of CMC is not inhibited by anti-measles virus antibody added to lymphocytes previously exposed to viral glycoproteins. The killer lymphocytes are Fc receptor positive, erythrocyte-rosetting and non-erythrocyte-rosetting, as assessed by positive and negative selection experiments. The induction of nonspecific CMC by viral glycoproteins in the soluble state or inserted into artificial membranes could be segregated from the CMC associated with whole virions. On kinetics studies, purified viral glycoproteins induced CMC more rapidly than did whole virions. Viral glycoprotein-produced response occurred in the absence of detectable release of interferon into the culture medium. CMC activity due to whole virions was associated with interferon release. The fact that purified measles virus glycoproteins integrated into artificial membrane bilayers were as efficient as their soluble counterparts in inducing CMC suggests that the hydrophobic portion of the glycoproteins was not involved in the induction and expression of the lytic activity. Purified glycoproteins from lymphocytic choriomeningitis virus behave similarly, although this virus is unrelated to measles virus. Interferon-independent CMC induced by viral glycoproteins might account for some of the biological reactions occurring early in the control of a viral infection.