Human Cytomegalovirus Infection of Caco-2 Cells Occurs at the Basolateral Membrane and is Differentiation State Dependent

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1999 May 11

PMID 10233913

Citations 28

Authors

M A Jarvis

C E Wang

H L MEYERS

P P Smith

C L Corless

G J Henderson

J Vieira

W J Britt

J A Nelson

Affiliations

Soon will be listed here.

Abstract

Epithelial cells are known to be a major target for human cytomegalovirus (HCMV) infection; however, the analysis of virus-cell interactions has been difficult to approach due to the lack of in vitro models. In this study, we established a polarized epithelial cell model using a colon epithelial cell-derived cell line (Caco-2) that is susceptible to HCMV infection at early stages of cellular differentiation. Infection of polarized cells was restricted to the basolateral surface whereas virus was released apically, which was consistent with the apical and not basolateral surface localization of two essential viral glycoproteins, gB and gH. HCMV infection resulted in the development of a cytopathology characteristic of HCMV infection of colon epithelium in vivo, and infection did not spread from cell to cell. The inability of HCMV to infect Caco-2 cells at late stages of differentiation was due to a restriction at the level of viral entry and was consistent with the sequestration of a cellular receptor for HCMV. These observations provide the first evidence that restriction of HCMV replication in epithelial cells is due to a receptor-mediated phenomenon.

Citing Articles

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References

Jeang K, Chin G, Hayward G . Characterization of cytomegalovirus immediate-early genes. I. Nonpermissive rodent cells overproduce the IE94K protein form CMV (Colburn). Virology. 1982; 121(2):393-403. DOI: 10.1016/0042-6822(82)90177-5. View

Vieira J, Schall T, Corey L, Geballe A . Functional analysis of the human cytomegalovirus US28 gene by insertion mutagenesis with the green fluorescent protein gene. J Virol. 1998; 72(10):8158-65. PMC: 110158. DOI: 10.1128/JVI.72.10.8158-8165.1998. View

Smith J . Human cytomegalovirus: demonstration of permissive epithelial cells and nonpermissive fibroblastic cells in a survey of human cell lines. J Virol. 1986; 60(2):583-8. PMC: 288929. DOI: 10.1128/JVI.60.2.583-588.1986. View

Nelson J, Groudine M . Transcriptional regulation of the human cytomegalovirus major immediate-early gene is associated with induction of DNase I-hypersensitive sites. Mol Cell Biol. 1986; 6(2):452-61. PMC: 367533. DOI: 10.1128/mcb.6.2.452-461.1986. View

Weinshenker B, Wilton S, Rice G . Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol. 1988; 140(5):1625-31. View

Uetsuki T, Naito A, Nagata S, Kaziro Y . Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha. J Biol Chem. 1989; 264(10):5791-8. View

Isola V, Eisenberg R, Siebert G, Heilman C, Wilcox W, Cohen G . Fine mapping of antigenic site II of herpes simplex virus glycoprotein D. J Virol. 1989; 63(5):2325-34. PMC: 250651. DOI: 10.1128/JVI.63.5.2325-2334.1989. View

Britt W, Vugler L, Butfiloski E, Stephens E . Cell surface expression of human cytomegalovirus (HCMV) gp55-116 (gB): use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response. J Virol. 1990; 64(3):1079-85. PMC: 249220. DOI: 10.1128/JVI.64.3.1079-1085.1990. View

Muggeridge M, Wu T, Johnson D, Glorioso J, Eisenberg R, Cohen G . Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D. Virology. 1990; 174(2):375-87. DOI: 10.1016/0042-6822(90)90091-5. View

10.

Jones T, Muzithras V . Fine mapping of transcripts expressed from the US6 gene family of human cytomegalovirus strain AD169. J Virol. 1991; 65(4):2024-36. PMC: 240048. DOI: 10.1128/JVI.65.4.2024-2036.1991. View

11.

Tanaka J, Sadanari H, Sato H, Fukuda S . Sodium butyrate-inducible replication of human cytomegalovirus in a human epithelial cell line. Virology. 1991; 185(1):271-80. DOI: 10.1016/0042-6822(91)90774-6. View

12.

Ibanez C, Schrier R, Ghazal P, Wiley C, Nelson J . Human cytomegalovirus productively infects primary differentiated macrophages. J Virol. 1991; 65(12):6581-8. PMC: 250717. DOI: 10.1128/JVI.65.12.6581-6588.1991. View

13.

Wagner B, Kropff B, Kalbacher H, Britt W, Sundqvist V, Ostberg L . A continuous sequence of more than 70 amino acids is essential for antibody binding to the dominant antigenic site of glycoprotein gp58 of human cytomegalovirus. J Virol. 1992; 66(9):5290-7. PMC: 289083. DOI: 10.1128/JVI.66.9.5290-5297.1992. View

14.

Compton T, Nowlin D, Cooper N . Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate. Virology. 1993; 193(2):834-41. DOI: 10.1006/viro.1993.1192. View

15.

Navarro D, Paz P, Tugizov S, Topp K, La Vail J, Pereira L . Glycoprotein B of human cytomegalovirus promotes virion penetration into cells, transmission of infection from cell to cell, and fusion of infected cells. Virology. 1993; 197(1):143-58. DOI: 10.1006/viro.1993.1575. View

16.

Molloy S, Thomas L, VanSlyke J, Stenberg P, Thomas G . Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. EMBO J. 1994; 13(1):18-33. PMC: 394775. DOI: 10.1002/j.1460-2075.1994.tb06231.x. View

17.

Fish K, Depto A, Moses A, Britt W, Nelson J . Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages. J Virol. 1995; 69(6):3737-43. PMC: 189090. DOI: 10.1128/JVI.69.6.3737-3743.1995. View

18.

Cha T, Tom E, Kemble G, Duke G, Mocarski E, Spaete R . Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J Virol. 1996; 70(1):78-83. PMC: 189790. DOI: 10.1128/JVI.70.1.78-83.1996. View

19.

Tugizov S, Maidji E, Pereira L . Role of apical and basolateral membranes in replication of human cytomegalovirus in polarized retinal pigment epithelial cells. J Gen Virol. 1996; 77 ( Pt 1):61-74. DOI: 10.1099/0022-1317-77-1-61. View

20.

Gaillard J, Finlay B . Effect of cell polarization and differentiation on entry of Listeria monocytogenes into the enterocyte-like Caco-2 cell line. Infect Immun. 1996; 64(4):1299-308. PMC: 173918. DOI: 10.1128/iai.64.4.1299-1308.1996. View