CoChat
Sign Up
Cited by 53

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells

Gruener, Myriam, Bravo, Ignacio G, Momburg, Frank, Alonso, Angel, Tomakidi, Pascal·2007·Virology Journal
DOI 10.1186/1743-422x-4-116PMC PMC2164959
Open this paper in CoChat — free account

Abstract

The human papillomavirus type 16 E5 protein (HPV16 E5) down-regulates surface expression of HLA-I molecules. The molecular mechanisms underlying this effect are so far unknown. Here we show that HPV16 E5 down-regulates HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. Immunoprecipitation experiments reveal that calnexin and HPV16E5 can be co-precipitated and that this association depends on the presence of a wild-type first hydrophobic region of E5. When an E5 mutant (M1) in which the first putative transmembrane helix had been disrupted was used for the transfections calnexin-E5 co-precipitation was strongly impaired. In addition, we show that the M1 mutant is only able to marginally down-regulate HLA-I surface expression compared to the wild-type protein. Besides, we demonstrate that E5 forms a ternary complex with calnexin and the heavy chain of HLA-I, which is mediated by the first hydrophobic region of the E5 protein. On the basis of our results we conclude that formation of this complex is responsible for retention of HLA-I molecules in the ER of the cells.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1743-422x-4-116

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 HPV16 E5 expression down-regulates HLA-I surface molecules. HEK-293T cells were transfected either with (A) pEGFP-HPV16-E5 or empty pEGFP vector, (B) pCI-HPV16-E5-HA or empty pCI vector. HLA-I molecules were then detected by immunostaining and flow cytometry using mouse monoclonal anti-HLA-A, B, C (mAb B9.12). Differences between the HLA-I surface expression levels were assessed by Kolmogorov-Smirnov test. This statistic defines the maximum vertical deviation between the two curves (pEGFP-E5 and GFP, pCI-E5-HA and pCI) as the statistic D. The p value of each single experiment was in all cases ≤ 0.001.
Figure 1 HPV16 E5 expression down-regulates HLA-I surface molecules. HEK-293T cells were transfected either with (A) pEGFP-HPV16-E5 or empty pEGFP vector, (B) pCI-HPV16-E5-HA or empty pCI vector. HLA-I molecules were then detected by immunostaining and flow cytometry using mouse monoclonal anti-HLA-A, B, C (mAb B9.12). Differences between the HLA-I surface expression levels were assessed by Kolmogorov-Smirnov test. This statistic defines the maximum vertical deviation between the two curves (pEGFP-E5 and GFP, pCI-E5-HA and pCI) as the statistic D. The p value of each single experiment was in all cases ≤ 0.001.CC BY · PubMed Central
Figure 2 HPV16 E5 decreases HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. CEM-C7 (calnexin) and CEM-NKR (no calnexin) cells were stably transfected with pCI-HPV16-E5-HA or pCI empty vector. A) Calnexin is only expressed in CEM-C7 cells but not in CEM-NKR cells. B) E5-HA expression was analysed in each stable polyclone by immunoprecipitation and -blot using mouse monoclonal anti-HA Ab and 500 μg RIPA cell lysate. C) FACS analysis of CEM-NKR and CEM-C7 cells transfected with either the empty vector pCI or with pCI-E5-HA were stained with anti-HLA-A, B, C mAbs B9.12. E5 expression results in diminished HLA-I surface staining in cells expressing calnexin, but not in calnexin deficient cells. D) The upper part of the blot shown in A was incubated with anti-HC-10 antibodies (anti HLA-B, C). Incubation with anti-actin antibodies was performed as loading control. Columns represent average values (N = 5) and the error bars comprise the corresponding standard deviations. There were no differences between the total amounts of cellular HLA (N = 5; pKW = 0.87, Kruskal-Wallis test, and pA = 0.77, ANOVA). Molecular-mass markers (in kDa) are indicated in the left of the blots.
Figure 2 HPV16 E5 decreases HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. CEM-C7 (calnexin) and CEM-NKR (no calnexin) cells were stably transfected with pCI-HPV16-E5-HA or pCI empty vector. A) Calnexin is only expressed in CEM-C7 cells but not in CEM-NKR cells. B) E5-HA expression was analysed in each stable polyclone by immunoprecipitation and -blot using mouse monoclonal anti-HA Ab and 500 μg RIPA cell lysate. C) FACS analysis of CEM-NKR and CEM-C7 cells transfected with either the empty vector pCI or with pCI-E5-HA were stained with anti-HLA-A, B, C mAbs B9.12. E5 expression results in diminished HLA-I surface staining in cells expressing calnexin, but not in calnexin deficient cells. D) The upper part of the blot shown in A was incubated with anti-HC-10 antibodies (anti HLA-B, C). Incubation with anti-actin antibodies was performed as loading control. Columns represent average values (N = 5) and the error bars comprise the corresponding standard deviations. There were no differences between the total amounts of cellular HLA (N = 5; pKW = 0.87, Kruskal-Wallis test, and pA = 0.77, ANOVA). Molecular-mass markers (in kDa) are indicated in the left of the blots.CC BY · PubMed Central
Figure 3 Transporter activity of TAP is not influenced by HPV16 E5. Streptolysin Opermeabilized calnexin-proficient CEM-C7 and calnexin-deficient CEM-NKR cells (38) were analysed in a peptide translocation/glyosylation assay using the indicated input quantities of the radioiodinated reporter peptide TNKTRIDGQY (glycosylation consensus site underlined) in the presence or absence of ATP. The glycosylated fraction, indicative of TAP-mediated ER transport, is isolated by concanavalin A Sepharose and quantitated by γ-counting. No significant differences could be detected between HPV16 E5-expressing cells and the control cells irrespective from the presence (CEM-C7) or absence (CEM-NKR) of calnexin.
Figure 3 Transporter activity of TAP is not influenced by HPV16 E5. Streptolysin Opermeabilized calnexin-proficient CEM-C7 and calnexin-deficient CEM-NKR cells (38) were analysed in a peptide translocation/glyosylation assay using the indicated input quantities of the radioiodinated reporter peptide TNKTRIDGQY (glycosylation consensus site underlined) in the presence or absence of ATP. The glycosylated fraction, indicative of TAP-mediated ER transport, is isolated by concanavalin A Sepharose and quantitated by γ-counting. No significant differences could be detected between HPV16 E5-expressing cells and the control cells irrespective from the presence (CEM-C7) or absence (CEM-NKR) of calnexin.CC BY · PubMed Central
Figure 4 Calnexin interacts with the HPV16 E5 protein in cellular extracts. HEK-293T cells were transfected with AU1-tagged codon-optimised HPV16 E5, pCI-HPV16-E5-HA or corresponding empty vectors and lysed at 24 h posttransfection with CHAPS lysis buffer. A) Immunoblot showing the expression levels of the codon-optimised E5 gene (left panel) and of the viral E5 gene (right panel). Note the differences in the immunoreactivity signals despite the higher amount of total protein loaded in the non-optimised gene (100 μg vs 30 μg). B) Immunoprecipitations were performed using monoclonal anti-E5-tag (AU1) antibodies and proteins in the immune complexes were probed using anti-AU1 and anti-calnexin antibodies. C) Immunoprecipitations were performed using monoclonal anti-calnexin antibodies and proteins in the immune complexes were probed using anti-calnexin and anti-E5-tag (AU1) anti-bodies. D) Immunoprecipitations were performed using monoclonal anti-E5-tag (HA) antibodies and proteins in the immune complexes were probed using anti-HA and anti-calnexin antibodies. E) 2 Immunoprecipitations were performed using monoclonal anti-calnexin antibodies and proteins in the immune complexes were probed using anti-calnexin and anti-E5-tag (HA) antibodies. Molecular-mass markers in kDa are indicated at the left of the blots.
Figure 4 Calnexin interacts with the HPV16 E5 protein in cellular extracts. HEK-293T cells were transfected with AU1-tagged codon-optimised HPV16 E5, pCI-HPV16-E5-HA or corresponding empty vectors and lysed at 24 h posttransfection with CHAPS lysis buffer. A) Immunoblot showing the expression levels of the codon-optimised E5 gene (left panel) and of the viral E5 gene (right panel). Note the differences in the immunoreactivity signals despite the higher amount of total protein loaded in the non-optimised gene (100 μg vs 30 μg). B) Immunoprecipitations were performed using monoclonal anti-E5-tag (AU1) antibodies and proteins in the immune complexes were probed using anti-AU1 and anti-calnexin antibodies. C) Immunoprecipitations were performed using monoclonal anti-calnexin antibodies and proteins in the immune complexes were probed using anti-calnexin and anti-E5-tag (AU1) anti-bodies. D) Immunoprecipitations were performed using monoclonal anti-E5-tag (HA) antibodies and proteins in the immune complexes were probed using anti-HA and anti-calnexin antibodies. E) 2 Immunoprecipitations were performed using monoclonal anti-calnexin antibodies and proteins in the immune complexes were probed using anti-calnexin and anti-E5-tag (HA) antibodies. Molecular-mass markers in kDa are indicated at the left of the blots.CC BY · PubMed Central
Figure 5 Co-localization of HPV16 E5 with calnexin. HaCaT cells were transfected with AU1- tagged codon-optimised E5 or pEGFP-E5 and analysed after 24 h by confocal laser scanning microscopy using a monoclonal anti-AU1 and/or polyclonal anti-calnexin Abs.
Figure 5 Co-localization of HPV16 E5 with calnexin. HaCaT cells were transfected with AU1- tagged codon-optimised E5 or pEGFP-E5 and analysed after 24 h by confocal laser scanning microscopy using a monoclonal anti-AU1 and/or polyclonal anti-calnexin Abs.CC BY · PubMed Central
Figure 6 Transmembrane Hidden Markov Model posterior probabilities for the sequences of E5 and the mutants M1, M2 and M3. A) Amino acid sequence of the wild-type E5 protein and corresponding mutants. Aminoacids of the AU1-tag are underlined. Arrows show the position of exchanged amino acids. B) Analysis of the wild-type E5 and mutants using the TMHMM 2.0 algorithm (36, 37), showing the three hydrophobic regions predicted to be transmembrane domains, and the corresponding disruptions in the three mutants.
Figure 6 Transmembrane Hidden Markov Model posterior probabilities for the sequences of E5 and the mutants M1, M2 and M3. A) Amino acid sequence of the wild-type E5 protein and corresponding mutants. Aminoacids of the AU1-tag are underlined. Arrows show the position of exchanged amino acids. B) Analysis of the wild-type E5 and mutants using the TMHMM 2.0 algorithm (36, 37), showing the three hydrophobic regions predicted to be transmembrane domains, and the corresponding disruptions in the three mutants.CC BY · PubMed Central
Figure 7 Mutant M1 binds less calnexin than wild-type E5 protein. HEK-293T cells were transfected with either (A-C) AU1-tagged codon-optimised HPV16 E5, the mutants M1, M2 and M3 or pcDNA 3.1 empty vector as control, (D and E) pEGFP-tagged HPV16 E5, mutant pEGFPM1, mock-control or pEGFP empty vector and lysed at 24 h posttransfection with CHAPS lysis buffer. A) Similar expression levels of all HPV16 E5 and the mutants M1, M2 and M3. B) Immunoprecipitations were performed using monoclonal anti-AU1, and proteins in the immune complex were detected using anti-AU1 and anti-calnexin. C) Quantification of co-precipitated calnexin for wild-type HPV16E5 protein, the mutants M1, M2, M3 and the vector control. The wild-type expression level was set to 100%. Data shown represent six independent experiments 2 plus standard errors of the mean. P values were calculated with paired two-tailed Student's t-test. D) Similar expression levels of pEGFP-HPV16-E5 and the mutant pEGFP-M1. E) Immunoprecipitations were performed using monoclonal anti-GFP, and proteins in the immune complex were detected using anti-GFP and anti-calnexin. Molecular-mass markers in kDa are indicated at the left of the blots.
Figure 7 Mutant M1 binds less calnexin than wild-type E5 protein. HEK-293T cells were transfected with either (A-C) AU1-tagged codon-optimised HPV16 E5, the mutants M1, M2 and M3 or pcDNA 3.1 empty vector as control, (D and E) pEGFP-tagged HPV16 E5, mutant pEGFPM1, mock-control or pEGFP empty vector and lysed at 24 h posttransfection with CHAPS lysis buffer. A) Similar expression levels of all HPV16 E5 and the mutants M1, M2 and M3. B) Immunoprecipitations were performed using monoclonal anti-AU1, and proteins in the immune complex were detected using anti-AU1 and anti-calnexin. C) Quantification of co-precipitated calnexin for wild-type HPV16E5 protein, the mutants M1, M2, M3 and the vector control. The wild-type expression level was set to 100%. Data shown represent six independent experiments 2 plus standard errors of the mean. P values were calculated with paired two-tailed Student's t-test. D) Similar expression levels of pEGFP-HPV16-E5 and the mutant pEGFP-M1. E) Immunoprecipitations were performed using monoclonal anti-GFP, and proteins in the immune complex were detected using anti-GFP and anti-calnexin. Molecular-mass markers in kDa are indicated at the left of the blots.CC BY · PubMed Central
Figure 8 HPV16 E5, M2 and M3 mutants but not M1 mutant strongly co-localize with calnexin. HaCaT cells were transfected with A) AU1-tagged codon-optimised E5 or AU1- tagged codonoptimised E5 mutants M1 B), M2 C), and M3 D) and analysed after 24 h by confocal laser scanning microscopy using a monoclonal anti-AU1 and polyclonal anticalnexin antibodies.
Figure 8 HPV16 E5, M2 and M3 mutants but not M1 mutant strongly co-localize with calnexin. HaCaT cells were transfected with A) AU1-tagged codon-optimised E5 or AU1- tagged codonoptimised E5 mutants M1 B), M2 C), and M3 D) and analysed after 24 h by confocal laser scanning microscopy using a monoclonal anti-AU1 and polyclonal anticalnexin antibodies.CC BY · PubMed Central
Figure 9 HPV16 E5 forms a ternary complex with calnexin and the HLA-I heavy chain. HeLa cells were transiently transfected with AU1-tagged codon-optimised HPV16 E5, M1, or empty vector. 24 h later CHAPS lysates were immunoprecipitated with antibodies against the E5-tag (anti-AU1). Precipitated immune complexes were separated by SDS-PAGE and Western blotted using anti-calnexin and anti-HLA-B, -C mAb (HC10), respectively (band marked with *). Molecular-mass markers in kDa are indicated at the left of the blots.
Figure 9 HPV16 E5 forms a ternary complex with calnexin and the HLA-I heavy chain. HeLa cells were transiently transfected with AU1-tagged codon-optimised HPV16 E5, M1, or empty vector. 24 h later CHAPS lysates were immunoprecipitated with antibodies against the E5-tag (anti-AU1). Precipitated immune complexes were separated by SDS-PAGE and Western blotted using anti-calnexin and anti-HLA-B, -C mAb (HC10), respectively (band marked with *). Molecular-mass markers in kDa are indicated at the left of the blots.CC BY · PubMed Central
Figure 10 E5 mutant M1 down-regulates surface expression of HLA-I to a lesser extent than the E5 protein does. HEK-293T cells were transfected either with pEGFP-HPV16- E5, -M1, or empty pEGFP vector. HLA-I molecules were detected by immunostaining and flow cytometry using mouse monoclonal anti-B9.12 Ab. Results for one representative experiment out of six are shown. Statistic analysis is shown in Table 1.
Figure 10 E5 mutant M1 down-regulates surface expression of HLA-I to a lesser extent than the E5 protein does. HEK-293T cells were transfected either with pEGFP-HPV16- E5, -M1, or empty pEGFP vector. HLA-I molecules were detected by immunostaining and flow cytometry using mouse monoclonal anti-B9.12 Ab. Results for one representative experiment out of six are shown. Statistic analysis is shown in Table 1.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 1 references

Research works printed but not linked: 55

  1. DiMaio D, Liao JB: Human papillomaviruses and cervical cancer. Adv Virus Res. 2006, 66: 125-159. · DOI
  2. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003, 348: 518-527. 10.1056/NEJMoa021641. · DOI · Paper page
  3. Franco EL, Schlecht NF, Saslow D: The epidemiology of cervical cancer. Cancer J. 2003, 9: 348-359. · DOI
  4. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999, 189: 12-19. 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. · DOI
  5. Clifford GM, Smith JS, Aguado T, Franceschi S: Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer. 2003, 89: 101-105. 10.1038/sj.bjc.6601024. · DOI
  6. Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002, 55: 244-265. · DOI
  7. Stoler MH, Broker TR: In situ hybridization detection of human papillomavirus DNAs and messenger RNAs in genital condylomas and a cervical carcinoma. Hum Pathol. 1986, 17: 1250-1258. · DOI
  8. Crum CP, Symbula M, Ward BE: Topography of early HPV 16 transcription in high-grade genital precancers. Am J Pathol. 1989, 134: 1183-1188.
  9. Garnett TO, Duerksen-Hughes PJ: Modulation of apoptosis by human papillomavirus (HPV) oncoproteins. Arch Virol. 2006, 151: 2321-2335. 10.1007/s00705-006-0821-0. · DOI
  10. Werness BA, Levine AJ, Howley PM: Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990, 248: 76-79. 10.1126/science.2157286. · DOI · Paper page
  11. Kabsch K, Alonso A: The human papillomavirus type 16 E5 protein impairs TRAIL- and FasL-mediated apoptosis in HaCaT cells by different mechanisms. J Virol. 2002, 76: 12162-12172. 10.1128/JVI.76.23.12162-12172.2002. · DOI
  12. Bravo IG, Crusius K, Alonso A: The E5 protein of human papillomavirus type 16 modulates composition and dynamics of membrane lipids in keratinocyte membranes. Arch Virol. 2005, 150: 231-246. 10.1007/s00705-004-0420-x. · DOI
  13. Sasagawa T, Inoue M, Tanizawa O, Yutsudo M, Hakura A: Identification of antibodies against human papillomavirus type 16 E6 and E7 proteins in sera of patients with cervical neoplasias. Jpn J Cancer Res. 1992, 83: 705-713. · DOI
  14. Muller M, Viscidi RP, Sun Y, Guerrero E, Hill PM, Shah F, Bosch FX, Munoz N, Gissmann L, Shah KV: Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer. Virology. 1992, 187: 508-514. 10.1016/0042-6822(92)90453-V. · DOI
  15. Dillner J: Mapping of linear epitopes of human papillomavirus type 16: the E1, E2, E4, E5, E6 and E7 open reading frames. Int J Cancer. 1990, 46: 703-711. 10.1002/ijc.2910460426. · DOI
  16. Kochel HG, Sievert K, Monazahian M, Mittelstadt-Deterding A, Teichmann A, Thomssen R: Antibodies to human papillomavirus type-16 in human sera as revealed by the use of prokaryotically expressed viral gene products. Virology. 1991, 182: 644-654. 10.1016/0042-6822(91)90605-B. · DOI
  17. Auvinen E, Crusius K, Steuer B, Alonso A: Human papillomavirus type 16 E5 protein (Review). Int J Oncol. 1997, 11: 1297-1304.
  18. O'Brien PM, Saveria Campo M: Evasion of host immunity directed by papillomavirus-encoded proteins. Virus Res. 2002, 88: 103-117. 10.1016/S0168-1702(02)00123-5. · DOI
  19. Zhang B, Li P, Wang E, Brahmi Z, Dunn KW, Blum JS, Roman A: The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-gamma. Virology. 2003, 310: 100-108. 10.1016/S0042-6822(03)00103-X. · DOI · Paper page
  20. Ashrafi GH, Haghshenas M, Marchetti B, Campo MS: E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domain. Int J Cancer. 2006, 119: 2105-2112. 10.1002/ijc.22089. · DOI · Paper page
  21. Ashrafi GH, Haghshenas MR, Marchetti B, O'Brien PM, Campo MS: E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I. Int J Cancer. 2005, 113: 276-283. 10.1002/ijc.20558. · DOI · Paper page
  22. Cromme FV, Snijders PJ, van den Brule AJ, Kenemans P, Meijer CJ, Walboomers JM: MHC class I expression in HPV 16 positive cervical carcinomas is post-transcriptionally controlled and independent from c-myc overexpression. Oncogene. 1993, 8: 2969-2975.
  23. Marchetti B, Ashrafi GH, Tsirimonaki E, O'Brien PM, Campo MS: The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface. Oncogene. 2002, 21: 7808-7816. 10.1038/sj.onc.1205885. · DOI
  24. Ortmann B, Androlewicz MJ, Cresswell P: MHC class I/beta 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature. 1994, 368: 864-867. 10.1038/368864a0. · DOI
  25. Ahluwalia N, Bergeron JJ, Wada I, Degen E, Williams DB: The p88 molecular chaperone is identical to the endoplasmic reticulum membrane protein, calnexin. J Biol Chem. 1992, 267: 10914-10918. · DOI
  26. Degen E, Cohen-Doyle MF, Williams DB: Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2-microglobulin and peptide. J Exp Med. 1992, 175: 1653-1661. 10.1084/jem.175.6.1653. · DOI
  27. Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ, Seliger B: Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol. 2001, 19: 1211-1220.
  28. Ayala-Torres S, Moller PC, Johnson BH, Thompson EB: Characteristics of 25-hydroxycholesterol-induced apoptosis in the human leukemic cell line CEM. Exp Cell Res. 1997, 235: 35-47. 10.1006/excr.1997.3630. · DOI
  29. Scott JE, Dawson JR: MHC class I expression and transport in a calnexin-deficient cell line. J Immunol. 1995, 155: 143-148. · DOI
  30. Howell DN, Andreotti PE, Dawson JR, Cresswell P: Natural killing target antigens as inducers of interferon: studies with an immunoselected, natural killing-resistant human T lymphoblastoid cell line. J Immunol. 1985, 134: 971-976. · DOI
  31. Bravo IG, Alonso A: Mucosal human papillomaviruses encode four different E5 proteins whose chemistry and phylogeny correlate with malignant or benign growth. J Virol. 2004, 78: 13613-13626. 10.1128/JVI.78.24.13613-13626.2004. · DOI · Paper page
  32. Oetke C, Auvinen E, Pawlita M, Alonso A: Human papillomavirus type 16 E5 protein localizes to the Golgi apparatus but does not grossly affect cellular glycosylation. Arch Virol. 2000, 145: 2183-2191. 10.1007/s007050070048. · DOI
  33. Gieswein CE, Sharom FJ, Wildeman AG: Oligomerization of the E5 protein of human papillomavirus type 16 occurs through multiple hydrophobic regions. Virology. 2003, 313: 415-426. 10.1016/S0042-6822(03)00296-4. · DOI · Paper page
  34. Rodriguez MI, Finbow ME, Alonso A: Binding of human papillomavirus 16 E5 to the 16 kDa subunit c (proteolipid) of the vacuolar H+-ATPase can be dissociated from the E5-mediated epidermal growth factor receptor overactivation. Oncogene. 2000, 19: 3727-3732. 10.1038/sj.onc.1203718. · DOI
  35. Yang DH, Wildeman AG, Sharom FJ: Overexpression, purification, and structural analysis of the hydrophobic E5 protein from human papillomavirus type 16. Protein Expr Purif. 2003, 30: 1-10. 10.1016/S1046-5928(03)00049-4. · DOI · Paper page
  36. Sonnhammer EL, von Heijne G, Krogh A: A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol. 1998, 6: 175-182.
  37. Moller S, Croning MD, Apweiler R: Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics. 2001, 17: 646-653. 10.1093/bioinformatics/17.7.646. · DOI
  38. Neefjes JJ, Momburg F, Hammerling GJ: Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science. 1993, 261: 769-771. 10.1126/science.8342042. · DOI
  39. Rebai N, Malissen B: Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies. Tissue Antigens. 1983, 22: 107-117. · DOI
  40. Ashrafi GH, Tsirimonaki E, Marchetti B, O'Brien PM, Sibbet GJ, Andrew L, Campo MS: Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins. Oncogene. 2002, 21: 248-259. 10.1038/sj.onc.1205008. · DOI
  41. Cartin W, Alonso A: The human papillomavirus HPV2a E5 protein localizes to the Golgi apparatus and modulates signal transduction. Virology. 2003, 314: 572-579. 10.1016/S0042-6822(03)00509-9. · DOI
  42. Foley GE, Lazarus H, Farber S, Uzman BG, Boone BA, McCarthy RE: Continuous Culture of Human Lymphoblasts from Peripheral Blood of a Child with Acute Leukemia. Cancer. 1965, 18: 522-529. 10.1002/1097-0142(196504)18:4<522::AID-CNCR2820180418>3.0.CO;2-J. · DOI
  43. Loch S, Tampe R: Viral evasion of the MHC class I antigen-processing machinery. Pflugers Arch. 2005, 451: 409-417. 10.1007/s00424-005-1420-8. · DOI
  44. Vossen MT, Westerhout EM, Soderberg-Naucler C, Wiertz EJ: Viral immune evasion: a masterpiece of evolution. Immunogenetics. 2002, 54: 527-542. 10.1007/s00251-002-0493-1. · DOI
  45. Zhou J, Liu WJ, Peng SW, Sun XY, Frazer I: Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability. J Virol. 1999, 73: 4972-4982. · DOI
  46. Leder C, Kleinschmidt JA, Wiethe C, Muller M: Enhancement of capsid gene expression: preparing the human papillomavirus type 16 major structural gene L1 for DNA vaccination purposes. J Virol. 2001, 75: 9201-9209. 10.1128/JVI.75.19.9201-9209.2001. · DOI
  47. Disbrow GL, Sunitha I, Baker CC, Hanover J, Schlegel R: Codon optimization of the HPV-16 E5 gene enhances protein expression. Virology. 2003, 311: 105-114. 10.1016/S0042-6822(03)00129-6. · DOI · Paper page
  48. Stam NJ, Spits H, Ploegh HL: Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol. 1986, 137: 2299-2306. · DOI
  49. Seliger B, Ritz U, Ferrone S: Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer. 2006, 118: 129-138. 10.1002/ijc.21312. · DOI
  50. Yewdell JW, Bennink JR: Mechanisms of viral interference with MHC class I antigen processing and presentation. Annu Rev Cell Dev Biol. 1999, 15: 579-606. 10.1146/annurev.cellbio.15.1.579. · DOI
  51. Vambutas A, DeVoti J, Pinn W, Steinberg BM, Bonagura VR: Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport. Clin Immunol. 2001, 101: 94-99. 10.1006/clim.2001.5094. · DOI
  52. Alonso A, Reed J: Modelling of the human papillomavirus type 16 E5 protein. Biochim Biophys Acta. 2002, 1601: 9-18. · DOI
  53. Bravo I, Alonso A, Auvinen E: Human papillomavirus type 16 E5 protein. Papillomavirus Report. 2004, 15: 1-6. 10.1179/095741904225004233. · DOI
  54. Cid-Arregui A, Juarez V, zur Hausen H: A synthetic E7 gene of human papillomavirus type 16 that yields enhanced expression of the protein in mammalian cells and is useful for DNA immunization studies. J Virol. 2003, 77: 4928-4937. 10.1128/JVI.77.8.4928-4937.2003. · DOI
  55. Samorski R, Gissmann L, Osen W: Codon optimized expression of HPV 16 E6 renders target cells susceptible to E6-specific CTL recognition. Immunol Lett. 2006, 107: 41-49. 10.1016/j.imlet.2006.07.003. · DOI

Cited by

See all 53

Metadata

Authors
Gruener, M., Bravo, I. G., Momburg, F., Alonso, A., & Tomakidi, P.
Venue
Virology Journal
Publisher
Springer Science and Business Media LLC
Published
2007-10-30
Volume
4
Issue
1
ISSN
1743-422X
DOI
10.1186/1743-422x-4-116
PMC
PMC2164959
Cited by
53
References
1
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells. https://app.cochat.ai/papers/10.1186/1743-422x-4-116
The paper
Gruener, M., Bravo, I. G., Momburg, F., Alonso, A., & Tomakidi, P. (2007). The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells. Virology Journal. https://doi.org/10.1186/1743-422x-4-116