Human Cytomegalovirus US3 Impairs Transport and Maturation of Major Histocompatibility Complex Class I Heavy Chains

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 Oct 15

PMID 8876135

Citations 145

Authors

T R Jones

E J Wiertz

L Sun

K N Fish

J A Nelson

H L Ploegh

Affiliations

Soon will be listed here.

Abstract

The human cytomegalovirus (HCMV) early glycoprotein products of the US11 and US2 open reading frames cause increased turnover of major histocompatibility complex (MHC) class I heavy chains. Since US2 is homologous to another HCMV gene (US3), we hypothesized that the US3 gene product also may affect MHC class I expression. In cells constitutively expressing the HCMV US3 gene, MHC class I heavy chains formed a stable complex with beta 2-microglobulin. However, maturation of the N-linked glycan of MHC class I heavy chains was impaired in US3+ cells. The glycoprotein product of US3 (gpUS3) occurs mostly in a high-mannose form and coimmunoprecipitates with beta 2-microglobulin associated class I heavy chains. Mature class I molecules were detected at steady state on the surface of US3+ cells, as in control cells. Substantial perinuclear accumulation of heavy chains was observed in US3+ cells. The data suggest that gpUS3 impairs egress of MHC class I heavy chains from the endoplasmic reticulum.

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References

Tenney D, Colberg-Poley A . Human cytomegalovirus UL36-38 and US3 immediate-early genes: temporally regulated expression of nuclear, cytoplasmic, and polysome-associated transcripts during infection. J Virol. 1991; 65(12):6724-34. PMC: 250752. DOI: 10.1128/JVI.65.12.6724-6734.1991. View

Oldstone M . Molecular anatomy of viral persistence. J Virol. 1991; 65(12):6381-6. PMC: 250674. DOI: 10.1128/JVI.65.12.6381-6386.1991. View

Jones T, Muzithras V . A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. J Virol. 1992; 66(4):2541-6. PMC: 289055. DOI: 10.1128/JVI.66.4.2541-2546.1992. View

Del Val M, Hengel H, Hacker H, Hartlaub U, Ruppert T, Lucin P . Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. J Exp Med. 1992; 176(3):729-38. PMC: 2119349. DOI: 10.1084/jem.176.3.729. View

Gooding L . Virus proteins that counteract host immune defenses. Cell. 1992; 71(1):5-7. DOI: 10.1016/0092-8674(92)90259-f. View

Hill A, Takiguchi M, McMichael A . Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the alpha 2 domain. Immunogenetics. 1993; 37(2):95-101. DOI: 10.1007/BF00216831. View

Hermiston T, Tripp R, Sparer T, Gooding L, Wold W . Deletion mutation analysis of the adenovirus type 2 E3-gp19K protein: identification of sequences within the endoplasmic reticulum lumenal domain that are required for class I antigen binding and protection from adenovirus-specific cytotoxic T.... J Virol. 1993; 67(9):5289-98. PMC: 237927. DOI: 10.1128/JVI.67.9.5289-5298.1993. View

Beersma M, Bijlmakers M, Ploegh H . Human cytomegalovirus down-regulates HLA class I expression by reducing the stability of class I H chains. J Immunol. 1993; 151(9):4455-64. View

CAMPBELL A, SLATER J . Down-regulation of major histocompatibility complex class I synthesis by murine cytomegalovirus early gene expression. J Virol. 1994; 68(3):1805-11. PMC: 236642. DOI: 10.1128/JVI.68.3.1805-1811.1994. View

10.

BEIER D, Cox J, Vining D, Cresswell P, Engelhard V . Association of human class I MHC alleles with the adenovirus E3/19K protein. J Immunol. 1994; 152(8):3862-72. View

11.

Warren A, Ducroq D, Lehner P, Borysiewicz L . Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes. J Virol. 1994; 68(5):2822-9. PMC: 236770. DOI: 10.1128/JVI.68.5.2822-2829.1994. View

12.

York I, Roop C, Andrews D, Riddell S, Graham F, Johnson D . A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994; 77(4):525-35. DOI: 10.1016/0092-8674(94)90215-1. View

13.

McFadden G, Kane K . How DNA viruses perturb functional MHC expression to alter immune recognition. Adv Cancer Res. 1994; 63:117-209. DOI: 10.1016/s0065-230x(08)60400-5. View

14.

Yamashita Y, Shimokata K, Saga S, Mizuno S, Tsurumi T, Nishiyama Y . Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells. J Virol. 1994; 68(12):7933-43. PMC: 237256. DOI: 10.1128/JVI.68.12.7933-7943.1994. View

15.

Hill A, Jugovic P, York I, Russ G, Bennink J, Yewdell J . Herpes simplex virus turns off the TAP to evade host immunity. Nature. 1995; 375(6530):411-5. DOI: 10.1038/375411a0. View

16.

Fruh K, Ahn K, Djaballah H, SEMPE P, van Endert P, Tampe R . A viral inhibitor of peptide transporters for antigen presentation. Nature. 1995; 375(6530):415-8. DOI: 10.1038/375415a0. View

17.

Levitskaya J, Coram M, Levitsky V, Imreh S, Klein G, Kurilla M . Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995; 375(6533):685-8. DOI: 10.1038/375685a0. View

18.

Jones T, Hanson L, Sun L, SLATER J, Stenberg R, CAMPBELL A . Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains. J Virol. 1995; 69(8):4830-41. PMC: 189296. DOI: 10.1128/JVI.69.8.4830-4841.1995. View

19.

Biegalke B . Regulation of human cytomegalovirus US3 gene transcription by a cis-repressive sequence. J Virol. 1995; 69(9):5362-7. PMC: 189377. DOI: 10.1128/JVI.69.9.5362-5367.1995. View

20.

Thale R, Szepan U, Hengel H, Geginat G, Lucin P, Koszinowski U . Identification of the mouse cytomegalovirus genomic region affecting major histocompatibility complex class I molecule transport. J Virol. 1995; 69(10):6098-105. PMC: 189506. DOI: 10.1128/JVI.69.10.6098-6105.1995. View