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J Virol, June 1998, p. 4650-4656, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evaluation of the Galalpha 1-3Gal Epitope as a Host Modification Factor Eliciting Natural Humoral Immunity to Enveloped Viruses

Raymond M. Welsh,1,* Carey L. O'Donnell,1 Deborah J. Reed,2 and Russell P. Rother2

Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655,1 and Department of Molecular Development, Alexion Pharmaceuticals, Inc., New Haven, Connecticut 065112

Received 17 November 1997/Accepted 23 February 1998

Human sera contain high levels of natural antibody (Ab) to Galalpha 1-3Gal, a terminal glycosidic structure expressed on the surface of cells of mammals other than Old World primates. Incorporation of this determinant onto retroviral membranes by passage of viruses in cells encoding alpha -1-3-galactosyltransferase (GT) renders retroviruses sensitive to lysis by natural Ab and complement in normal human serum (NHS). Plasma membrane-budding viruses representing four additional virus groups were examined for their sensitivities to serum inactivation after passage through human cell lines that lack a functional GT or human cells expressing recombinant porcine GT. The inactivation of lymphocytic choriomeningitis virus (LCMV) by NHS directly correlated with host modification of the virus via expression of Galalpha 1-3Gal and was blocked by incorporation of soluble Galalpha 1-3Gal disaccharide into the inactivation assay. GT-deficient mice immunized to make high levels of Ab to Galalpha 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 antiviral activity of the sera was insufficient to eliminate LCMV infectivity on its natural targets of infection, macrophages, which express receptors for Ab and complement. Newcastle disease virus and vesicular stomatitis virus (VSV) were inactivated by NHS regardless of cell passage history, whereas Sindbis virus (SV) passaged in human cells resisted inactivation. Both VSV and SV passaged in Galalpha 1-3Gal-expressing human cells incorporated this sugar moiety onto their major envelope glycoproteins. SV passaged in mouse cells expressing Galalpha 1-3Gal was moderately sensitive to inactivation by NHS. These results indicate that enveloped viruses expressing Galalpha 1-3Gal differ in their sensitivities to NHS and that a potent complement source, such as that in NHS, is required for efficient inactivation of sensitive viruses in vitro and in vivo.

* Corresponding author. Mailing address: Department of Pathology, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-5819. Fax: (508) 856-5780. E-mail: rwelsh{at}bangate.ummed.edu.

J Virol, June 1998, p. 4650-4656, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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