Bombyx mori nuclear polyhedrosis virus infection regulated by host glycosphingolipids

Abstract

Glycosylation is an important post-translational modification commonly found in eukaryotes, and plays crucial roles in many biological activities. The silkworm Bombyx mori (B. mori), an important economic insect and a model organism in biology, has recently been found to be abundantly glycosylated. In this study, we established the role of silkworm glycosphingolipids (GSLs), the glycoconjugates formed by covalent attachment of a glycan to the lipid class of ceramide, during B. mori nuclear polyhedrosis virus (BmNPV) infection. The levels of cellular glycosphingolipids (GSLs), particularly the glucosylceramide (Glc-Cer) series, were modulated by targeting uridine diphosphate-glucose ceramide glycosyltransferase (UGCG), the enzyme responsible for Glc-Cer synthesis. Inhibiting UGCG activity by Genz-123346 (Genz), an inhibitor and substrate analogue of UGCG, reduced BmNPV binding, internalization, and viral protein expression in BmN cells. A general reduction in the cellular GSL contents was observed following Genz treatment. Overexpression of UGCG increased cellular GSL levels overall while still caused suppression in viral infection. It is postulated that GSLs are highly regulated membrane components that are crucial for viral entry, and disturbing the balance, either by increasing or decreasing cellular GSL components, alters membrane traffic and transport, which is unfavorable for viral infection. Therefore, highly regulated cellular GSLs are required for effective BmNPV infection. This study provides direct evidence linking GSL levels to BmNPV infection, offering new insights into the role of GSLs in viral infection.