Effect of tunicamycin and monensin on biosynthesis, transport, and maturation of bovine herpesvirus type-1 glycoproteins

Abstract

The effect of tunicamycin and monensin on the biosynthesis, intracellular transport, and maturation of bovine herpesvirus type-1 (BHV-1) glycoproteins was examined. Tunicamycin completely inhibited the production of infectious virus particles and significantly reduced the incorporation of [3H]glucosamine into viral glycoproteins. In the presence of monensin, reduced amounts of infectious virus particles were produced, which was mainly due to inhibition of virus release, rather than virus production. Monensin only slightly inhibited viral glycoprotein synthesis. The effects of these compounds on infectivity indicated that glycosylation is required for the production of infectious virus, though complete processing of the glycoproteins is not essential. In addition, egress of the virions from infected cells probably requires a functional Golgi complex. In the presence of tunicamycin or monensin various degrees of glycosylation of the major glycoproteins occurred, consequently their rates of migration differed from that of the normal glycoproteins. Tunicamycin completely blocked glycosylation of GVP 6/11a/16 and GVP 7. In contrast, GVP 3/9 and GVP 11b were partially glycosylated in the presence of tunicamycin. These results indicated that GVP 6/11a/16 and GVP 7 are N-linked glycoproteins, but GVP 3/9 and GVP 11b contain both N- and O-linked oligosaccharide side chains. Tunicamycin blocked the transport of all viral glycoproteins to the cell surface, suggesting that glycosylation is required for this process. In the presence of monensin, the viral glycoproteins were transported and expressed on the cell surface indicating that transport does not require complete processing of the glycoproteins and may occur via a Golgi-independent pathway. In addition, monensin-treated BHV-1 infected cells could act as target cells in an antibody-dependent cell cytotoxicity assay. Thus, complete glycosylation may not be essential for maintenance of antigenicity and participation in immune destruction.

Bovine herpesvirus type 1 gp87 mediates both attachment of virions to susceptible cells and hemagglutination

“…BHV-1 specifies at least three glycopr0teins with molecular weights of 117-130kd (a disulfide-linked complex composed of two different sized subunits), 87-97kd (which possibly forms a dimer), and 71-105kd, each of which induces the corresponding neutralizing antibodies [4,6,25,31,42]. These glycoproteins have also been reported to be involved in an-tibody and complement-mediated cytolysis [27, 421 and antibody-dependent cell-mediated cytotoxicity [41 ]. The glycoproteins are thus maj or targets of immune response and are assumed to play important roles in infection, although none of them have been well defined with regard to function, despite the existence of a certain amount of suggestive evidence [31,32,42].…”

Herpes Simplex Virus Type 1 Capsids Transit by the trans -Golgi Network, Where Viral Glycoproteins Accumulate Independently of Capsid Egress

“…Various inhibitors of this pathway have been used in the past to perturb cellular and viral glycoproteins transport, including monensin (44,88), tunicamycin (65,88), and brefeldin A (18,92). Furthermore, intracellular transport is a temperature-dependent process.…”

Mode of action of a new type of UDP-glucose analog against herpesvirus replication

“…It is difficult to define which of the above-described steps is directly responsible for the observed inhibition of viral replication, but we can argue that the blockade of nucleic acid synthesis must be crucial in this respect, because inhibitors of glycosylation allow the synthesis of late herpesvirus proteins to take place. Even new virions are formed in the presence of tunicamycin or 2-deoxy-glucose, although the lack of proper glycosylation of their proteins makes them noninfectious (9,13,15,17). It is also interesting to mention the finding that the potent antiviral agent bromovinyldeoxyuridine, in addition to interfering with viral DNA synthesis, blocks protein glycosylation (11).…”