EVALUATION OF THE GAL-ALPHA-1-3GAL EPITOPE AS A HOST MODIFICATION FACTOR ELICITING NATURAL HUMORAL IMMUNITY TO ENVELOPED VIRUSES

Human sera contain high levels of natural antibody (Ab) to Gal alpha 1 -3Gal, a terminal glycosidic structure expressed on the surface of cel ls of mammals other than Old World primates. Incorporation of this det erminant onto retroviral membranes by passage of viruses in cells enco ding alpha-1-3-galactosyltransferase (GT) renders retroviruses sensiti ve to lysis by natural Ab and complement in normal human serum (MHS), Plasma membrane-budding viruses representing four additional virus gro ups were examined for their sensitivities to serum inactivation after passage through human cell lines that lack a functional GT or human ce lls expressing recombinant porcine GT. The inactivation of lymphocytic choriomeningitis virus (LCMV) by NHS directly correlated with host mo dification of the virus via expression of Gal alpha 1-3Gal and was blo cked by incorporation of soluble Gal alpha 1-3Gal disaccharide into th e inactivation assay. GT-deficient mice immunized to make high levels of Ab to Gal alpha 1-3Gal (anti-Gal Ab) were tested for resistance to LCMV passaged in GT-expressing cells. Resistance was not observed, but in vitro analyses of the mouse immune sera revealed that the antivira l activity of the sera was insufficient to eliminate LCMV infectivity on its natural targets of infection, macrophages, which express recept ors for Ab and complement. Newcastle disease virus and vesicular stoma titis virus (VSV) were inactivated by NHS regardless of cell passage h istory, whereas Sindbis virus (SV) passaged in human cells resisted in activation. Both VSV and SV passaged in Gal alpha 1-3Gal-expressing hu man cells incorporated this sugar moiety onto their major envelope gly coproteins. SV passaged in mouse cells expressing Gal alpha 1-3Gal was moderately sensitive to inactivation by NHS. These results indicate t hat enveloped viruses expressing Gal alpha 1-3Gal differ in their sens itivities to NHS and that a potent complement source, such as that in NHS, is required for efficient inactivation of sensitive viruses in vi tro and in vivo.