Abstract
Varicella-zoster virus (VZV)-infected human embryonic lung fibroblasts (HELF) do not release infectious virions into their growth medium. Extracellular virions are pleomorphic, suggesting that they are partially degraded before their release from cells. To examine the intracellular pathway of viral maturation, [2-3H]mannose-labeled virus-encoded glycoproteins were isolated from VZV-infected HELF. Oligosaccharides attached to the glycoproteins were processed to complex-type units, some of which were phosphorylated. The major intracellular site of accumulation of VZV gpI was found to be perinuclear and to correspond to that of the cation-independent mannose 6-phosphate (Man 6-P) receptor. Subsets of VZV-containing cytoplasmic vacuoles were coated, Golgi-associated, or accessible to endocytic tracers. Phosphorylated monosaccharides protected HELF from the cytopathic effect of VZV in proportion to their ability to block Man 6-P receptor-mediated endocytosis. These data suggest that the unusual phosphorylated oligosaccharides mediate an interaction between VZV and Man 6-P receptors of the host cell; this interaction may be responsible for withdrawal of newly synthesized virions from the secretory pathway and for their diversion to prelysosomal structures.
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Selected References
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- Anderson R. G., Pathak R. K. Vesicles and cisternae in the trans Golgi apparatus of human fibroblasts are acidic compartments. Cell. 1985 Mar;40(3):635–643. doi: 10.1016/0092-8674(85)90212-0. [DOI] [PubMed] [Google Scholar]
- Brown W. J., Goodhouse J., Farquhar M. G. Mannose-6-phosphate receptors for lysosomal enzymes cycle between the Golgi complex and endosomes. J Cell Biol. 1986 Oct;103(4):1235–1247. doi: 10.1083/jcb.103.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Compton T., Courtney R. J. Virus-specific glycoproteins associated with the nuclear fraction of herpes simplex virus type 1-infected cells. J Virol. 1984 Feb;49(2):594–597. doi: 10.1128/jvi.49.2.594-597.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cook M. L., Stevens J. G. Labile coat: reason for noninfectious cell-free varicella-zoster virus in culture. J Virol. 1968 Dec;2(12):1458–1464. doi: 10.1128/jvi.2.12.1458-1464.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croze E. M., Morré D. J., Morré D. M., Kartenbeck J., Franke W. W. Distribution of clathrin and spiny-coated vesicles on membranes within mature Golgi apparatus elements of mouse liver. Eur J Cell Biol. 1982 Aug;28(1):130–138. [PubMed] [Google Scholar]
- Cummings R. D., Kornfeld S. Fractionation of asparagine-linked oligosaccharides by serial lectin-Agarose affinity chromatography. A rapid, sensitive, and specific technique. J Biol Chem. 1982 Oct 10;257(19):11235–11240. [PubMed] [Google Scholar]
- Cummings R. D., Kornfeld S., Schneider W. J., Hobgood K. K., Tolleshaug H., Brown M. S., Goldstein J. L. Biosynthesis of N- and O-linked oligosaccharides of the low density lipoprotein receptor. J Biol Chem. 1983 Dec 25;258(24):15261–15273. [PubMed] [Google Scholar]
- Duncan J. R., Kornfeld S. Intracellular movement of two mannose 6-phosphate receptors: return to the Golgi apparatus. J Cell Biol. 1988 Mar;106(3):617–628. doi: 10.1083/jcb.106.3.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gabel C. A., Foster S. A. Postendocytic maturation of acid hydrolases: evidence of prelysosomal processing. J Cell Biol. 1987 Oct;105(4):1561–1570. doi: 10.1083/jcb.105.4.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gabel C. A., Goldberg D. E., Kornfeld S. Lysosomal enzyme oligosaccharide phosphorylation in mouse lymphoma cells: specificity and kinetics of binding to the mannose 6-phosphate receptor in vivo. J Cell Biol. 1982 Nov;95(2 Pt 1):536–542. doi: 10.1083/jcb.95.2.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gershon A., Cosio L., Brunell P. A. Observations on the growth of varicella-zoster virus in human diploid cells. J Gen Virol. 1973 Jan;18(1):21–31. doi: 10.1099/0022-1317-18-1-21. [DOI] [PubMed] [Google Scholar]
- Geuze H. J., Slot J. W., Strous G. J., Hasilik A., von Figura K. Possible pathways for lysosomal enzyme delivery. J Cell Biol. 1985 Dec;101(6):2253–2262. doi: 10.1083/jcb.101.6.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghosh-Choudhury N., Graham A., Ghosh H. P. Herpes simplex virus type 2 glycoprotein biogenesis: effect of monensin on glycoprotein maturation, intracellular transport and virus infectivity. J Gen Virol. 1987 Jul;68(Pt 7):1939–1949. doi: 10.1099/0022-1317-68-7-1939. [DOI] [PubMed] [Google Scholar]
- Gonzalez-Noriega A., Grubb J. H., Talkad V., Sly W. S. Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J Cell Biol. 1980 Jun;85(3):839–852. doi: 10.1083/jcb.85.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Griffiths G., Hoflack B., Simons K., Mellman I., Kornfeld S. The mannose 6-phosphate receptor and the biogenesis of lysosomes. Cell. 1988 Feb 12;52(3):329–341. doi: 10.1016/s0092-8674(88)80026-6. [DOI] [PubMed] [Google Scholar]
- Griffiths G., Pfeiffer S., Simons K., Matlin K. Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane. J Cell Biol. 1985 Sep;101(3):949–964. doi: 10.1083/jcb.101.3.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grose C., Edwards D. P., Friedrichs W. E., Weigle K. A., McGuire W. L. Monoclonal antibodies against three major glycoproteins of varicella-zoster virus. Infect Immun. 1983 Apr;40(1):381–388. doi: 10.1128/iai.40.1.381-388.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herzog V., Neumüller W., Holzmann B. Thyroglobulin, the major and obligatory exportable protein of thyroid follicle cells, carries the lysosomal recognition marker mannose-6-phosphate. EMBO J. 1987 Mar;6(3):555–560. doi: 10.1002/j.1460-2075.1987.tb04790.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones F., Grose C. Role of cytoplasmic vacuoles in varicella-zoster virus glycoprotein trafficking and virion envelopment. J Virol. 1988 Aug;62(8):2701–2711. doi: 10.1128/jvi.62.8.2701-2711.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan A., Achord D. T., Sly W. S. Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc Natl Acad Sci U S A. 1977 May;74(5):2026–2030. doi: 10.1073/pnas.74.5.2026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly R. B. Pathways of protein secretion in eukaryotes. Science. 1985 Oct 4;230(4721):25–32. doi: 10.1126/science.2994224. [DOI] [PubMed] [Google Scholar]
- Kornfeld K., Reitman M. L., Kornfeld R. The carbohydrate-binding specificity of pea and lentil lectins. Fucose is an important determinant. J Biol Chem. 1981 Jul 10;256(13):6633–6640. [PubMed] [Google Scholar]
- Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
- Kornfeld S. Trafficking of lysosomal enzymes. FASEB J. 1987 Dec;1(6):462–468. doi: 10.1096/fasebj.1.6.3315809. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lazzarino D. A., Gabel C. A. Biosynthesis of the mannose 6-phosphate recognition marker in transport-impaired mouse lymphoma cells. Demonstration of a two-step phosphorylation. J Biol Chem. 1988 Jul 25;263(21):10118–10126. [PubMed] [Google Scholar]
- McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
- Montalvo E. A., Grose C. Assembly and processing of the disulfide-linked varicella-zoster virus glycoprotein gpII(140). J Virol. 1987 Sep;61(9):2877–2884. doi: 10.1128/jvi.61.9.2877-2884.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montalvo E. A., Parmley R. T., Grose C. Structural analysis of the varicella-zoster virus gp98-gp62 complex: posttranslational addition of N-linked and O-linked oligosaccharide moieties. J Virol. 1985 Mar;53(3):761–770. doi: 10.1128/jvi.53.3.761-770.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Namazue J., Campo-Vera H., Kitamura K., Okuno T., Yamanishi K. Processing of virus-specific glycoproteins of varicella zoster virus. Virology. 1985 May;143(1):252–259. doi: 10.1016/0042-6822(85)90112-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okuno T., Yamanishi K., Shiraki K., Takahashi M. Synthesis and processing of glycoproteins of Varicella-Zoster virus (VZV) as studied with monoclonal antibodies to VZV antigens. Virology. 1983 Sep;129(2):357–368. doi: 10.1016/0042-6822(83)90175-7. [DOI] [PubMed] [Google Scholar]
- Poliquin L., Levine G., Shore G. C. Involvement of Golgi apparatus and a restructured nuclear envelope during biogenesis and transport of herpes simplex virus glycoproteins. J Histochem Cytochem. 1985 Sep;33(9):875–883. doi: 10.1177/33.9.2991363. [DOI] [PubMed] [Google Scholar]
- Reitman M. L., Varki A., Kornfeld S. Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5'-diphosphate-N-acetylglucosamine: glycoprotein N-acetylglucosaminylphosphotransferase activity. J Clin Invest. 1981 May;67(5):1574–1579. doi: 10.1172/JCI110189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenfeld M. G., Kreibich G., Popov D., Kato K., Sabatini D. D. Biosynthesis of lysosomal hydrolases: their synthesis in bound polysomes and the role of co- and post-translational processing in determining their subcellular distribution. J Cell Biol. 1982 Apr;93(1):135–143. doi: 10.1083/jcb.93.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saraste J., Kuismanen E. Pre- and post-Golgi vacuoles operate in the transport of Semliki Forest virus membrane glycoproteins to the cell surface. Cell. 1984 Sep;38(2):535–549. doi: 10.1016/0092-8674(84)90508-7. [DOI] [PubMed] [Google Scholar]
- Saraste J., Palade G. E., Farquhar M. G. Temperature-sensitive steps in the transport of secretory proteins through the Golgi complex in exocrine pancreatic cells. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6425–6429. doi: 10.1073/pnas.83.17.6425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiraki K., Takahashi M. Virus particles and glycoprotein excreted from cultured cells infected with varicella-zoster virus (VZV). J Gen Virol. 1982 Aug;61(Pt 2):271–275. doi: 10.1099/0022-1317-61-2-271. [DOI] [PubMed] [Google Scholar]
- Sly W. S., Fischer H. D. The phosphomannosyl recognition system for intracellular and intercellular transport of lysosomal enzymes. J Cell Biochem. 1982;18(1):67–85. doi: 10.1002/jcb.1982.240180107. [DOI] [PubMed] [Google Scholar]
- Steinman R. M., Silver J. M., Cohn Z. A. Pinocytosis in fibroblasts. Quantitative studies in vitro. J Cell Biol. 1974 Dec;63(3):949–969. doi: 10.1083/jcb.63.3.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TAYLOR-ROBINSON D. Chickenpox and herpes zoster. III. Tissue culture studies. Br J Exp Pathol. 1959 Dec;40:521–532. [PMC free article] [PubMed] [Google Scholar]
- Tarentino A. L., Gómez C. M., Plummer T. H., Jr Deglycosylation of asparagine-linked glycans by peptide:N-glycosidase F. Biochemistry. 1985 Aug 13;24(17):4665–4671. doi: 10.1021/bi00338a028. [DOI] [PubMed] [Google Scholar]
- Tycko B., Maxfield F. R. Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin. Cell. 1982 Mar;28(3):643–651. doi: 10.1016/0092-8674(82)90219-7. [DOI] [PubMed] [Google Scholar]
- Varki A., Kornfeld S. Structural studies of phosphorylated high mannose-type oligosaccharides. J Biol Chem. 1980 Nov 25;255(22):10847–10858. [PubMed] [Google Scholar]
- von Figura K., Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. doi: 10.1146/annurev.bi.55.070186.001123. [DOI] [PubMed] [Google Scholar]