Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase

Abstract

Human immunodeficiency virus (HIV), the causative agent of AIDS, infects human lymphocytes and monocytes^1,2. An interaction between the viral envelope gp120 and CD4 protein is required to initiate an infectious cycle^3–7. HIV infection in vitro induces syncytium formation by cell-to-cell fusion; this aspect of viral cytopathogenicity is even more dependent on gp120–CD4 interactions⁴. That gp120 is extremely heavily glycosylated (31–36 N-linked glycans per molecule), suggests involvement of N-linked glycans in the gp120–CD4 interaction⁸. We therefore investigated the effects of castanospermine, 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM), three trimming glycosidase inhibitors which perturb N-linked glycan structure⁹, on induction of the formation of syncytium between HIV-infected and CD4-expressing cells. The glucosidase inhibitors castanospermine and dNM, but not the mannosidase inhibitor dMM, inhibited syncytium formation and interfered with infectivity. The potential of glucosidase inhibitors as anti-HIV therapeutic agents deserves further investigation, especially because dNM and related compounds show little toxicity in vitro and in vivo^9–11.