Effects of 2-deoxyglucose, glucosamine, and mannose on cell fusion and the glycoproteins of herpes simplex virus

Abstract

2-Deoxyglucose and glucosamine were found to inhibit cell fusion caused by a syncytial mutant of herpes simplex virus and to inhibit the glycosylation of viral glycoproteins in the infected cells. The inhibition of fusion and the inhibition of glycosylation caused by 2-deoxyglucose were substantially prevented when mannose was also present during infection. When glycosylation was inhibited, three new bands were found in the major glycoprotein region on sodium dodecyl sulfate-polyacrylamide gels. These bands may be precursors to the normal glycoproteins. The correlation between fusion and glycosylation in the presence of 2-deoxyglucose, glucosamine, and mannose suggests that the cells cannot fuse if their glycoproteins have a considerably reduced carbohydrate content.

Requirement for hexose, unrelated to energy provision, in T-cell-mediated cytolysis at the lethal hit stage.

“…Mannose, as well as glucose, was found by MacDonald to reverse the 2-deoxy-D-glucose block of T-cell-mediated cytolysis (6). It has been shown that 2-deoxy-D-glucose interferes with virus-induced cell fusion (39). This effect is also reversed by mannose and glucose.…”

Inhibitors of protein glycosylation and glycoprotein processing in viral systems

“…Thus, synthesis, transport to intraceUular localization of virus budding, and proper function of the viral cell-attachment component appear not to be dependent on presence of Nlinked oligosaccharides. In contrast, the fusion activity of HSV glycoproteins must be abolished by the absence of N-linked oligosaccharides (Knowles and Person, 1976).…”

Inhibition of the Multiplication of Enveloped and Non-enveloped Viruses by Glucosamine

“…This finding may rule out a nonspecific antiviral effect of GN, because a viral-induced cytopathogenic effect is still able to develop after a well defined period of incubation. In the case of enveloped viruses the inhibition of the cytopathogenic effect caused by G N could be explained, as currently suggested, by an impairment of the synthesis of the envelope glycoproteins (Scholtissek 1975;Kaluza 1975;Knowles & Person 1976). In the case of adenovirus, which is not an enveloped virus, it may be argued that GN may impair the synthesis of the capsidial glycoprotein.…”