Sensitization of cells and retroviruses to human serum by (alpha 1-3) galactosyltransferase

Mammalian C-type retroviruses are inactivated by human serum, following triggering of the classical complement cascade. This may have inhibited transmission to humans of C-type oncoviruses from other mammals. Indeed, the retroviruses human immunodeficiency virus and human T-cell leukaemia virus are resistant to human complement. Antibody-independent activation of human C1q, the first component of the classical pathway, by retroviral envelope proteins has been described. However, retroviruses produced from human cells are resistant to inactivation by human complement and human serum is known to contain antibodies directed against carbohydrates on retroviral envelopes. Gal(alpha 1-3)Gal terminal carbohydrates are expressed by most mammals but are absent in humans, which lack a functional (alpha 1-3)galactosyltransferase gene. Here, we demonstrate that anti-Gal(alpha 1-3)Gal antibodies in human serum inactivate retroviruses produced from animal cells. Expression of porcine (alpha 1-3)galactosyltransferase in human cells renders the cells and the retroviruses they produce sensitive to human serum.