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Varicella-zoster virus (VZV) is a highly virulent, disease-producing agent; nevertheless, the virus is cell-associated and difficult to grow in vitro. 1 This paradoxical behavior is reflected in the difference in the appearance of virions in vivo and in vitro. VZV particles in vesicle fluid from patients are well formed, enveloped, and infectious. In contrast, VZV particles in culture media withdrawn from infected cells are structurally damaged and not infectious. The appearance of the virions in media suggests that cultured cells might digest VZV intracellularly before the virions are secreted. 2 Indeed, electron microscopic (EM) observations have revealed that enveloped virions accumulate in intracellular vacuoles that contain the lysosomal enzyme, acid phosphatase, which could account for their degradation prior to release. 2 The coincident targeting of VZV and a lysosomal enzyme to the same intracellular destination raised the possibility that VZV, like lysosomal enzymes, 3 is diverted from the secretory pathway by binding to one of the mannose 6-phosphate receptors (MPRs). Since mannose 6-phosphate (Man 6-P) residues are present in the oligosaccharides of the envelope glycoproteins of VZV, 4 an interaction between VZV and an MPR is theoretically possible. The MPRs cycle in cells and follow an itinerary with stops in the trans-Golgi network (TGN), prelysosomes (late endosomes), and the plasma membrane. 3 Experimental observations have been consistent with the hypothesis that interaction of cell-free VZV with a plasmalemmal MPR plays a role in mediating viral entry into target cells. 4 Infection of human embryonic lung fibroblasts (HELF) by cell-free preparations of VZV is inhibited by Man 6-P and other phosphorylated monosaccharides with an order of potency that parallels their affinity for MPRs. 4 Treatment of cells with chloroquine, which prevents the MPRs from cycling to the cell surface, protects them from infection by VZV; moreover, cell-free VZV rapidly loses its …
Zhu et al. (Fri,) studied this question.