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Animal: DNA Viruses |
Department of Microbiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan1
Department of Pathology2 and Institute of Infectious Diseases3, University of Milan, ‘L. Sacco’ Hospital, Milan, Italy
Author for correspondence: Koichi Yamanishi. Fax +81 6 6879 3329. e-mail yamanisi{at}micro.med.osaka-u.ac.jp
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). Sero-epidemiological studies have demonstrated that KSHV infection is tightly linked to KS risk (Gao et al., 1996 ; Simpson et al., 1996 ) and that this virus infection is associated with two other AIDS-related diseases, primary effusion lymphoma (PEL) (Cesarman et al., 1995 ) and multicentric Castleman’s disease (MCD) (Soulier et al., 1995 ). Several cell lines have been established from patients with human immunodeficiency virus (HIV)-negative or -positive body cavity-based lymphoma, including BC-3 and BCBL-1 cells (Arvanitakis et al., 1996 ; Renne et al., 1996 ), and viral gene expression is highly restricted in these cells. Following treatment of these cells with sodium butyrate or 12-O-tetradecanoylphorbol 13-acetate (TPA), a cascade of viral gene expression is induced, resulting in lytic replication of the virus (Miller et al., 1996 , 1997 ).
In general, viral gene products influence the normal expression of cellular genes. One such example of altered gene expression is the down-regulation of the major histocompatibility complex class I (MHC-I) at the cell surface. This has been well studied in cells that have been infected or transfected with adenovirus (Andersson et al., 1985 ; Burgert & Kvist, 1985 ), herpes simplex virus (HSV) (Jennings et al., 1985 ), human cytomegalovirus (HCMV) (Jones et al., 1996 ; Lehner et al., 1997 ; Wiertz et al., 1996 ), murine cytomegalovirus (MCMV) (Campbell & Slater, 1994 ) and HIV (Schwartz et al., 1996 ).
Our first attempt was to demonstrate the decrease of MHC-I expression in cells infected with KSHV as well as cells transfected with K5 gene. We previously reported that K5 is an endoplasmic reticulum (ER) resident protein (Haque et al., 2000 ). Since ER resident proteins of other viruses have been shown to down-regulate MHC-I molecules, we designed experiments to examine whether the K5 gene product could down-regulate MHC-I molecules. BC-3 cells treated with TPA for 6, 12 and 24 h, and HeLa cells at 24 h post-transfection, were harvested and processed for FACS analysis with a fluorescent isothiocyanate (FITC)-labelled anti-HLA-A, B, C monoclonal antibody (MAb), W6/32 (Dako). Using MAb to K5 protein (Haque et al., 2000 ), we first examined the cells by immunofluorescent antibody (IFA) test. As shown in Fig. 1(A), about 10–15% of the cells expressed the K5 protein by 6 h after treatment with 20 ng/ml TPA (Fig. 1A, panel a). The percentage of positive cells increased to 40–50% by 12 h (Fig. 1A, panel b) and almost all cells were positive 24 h after treatment (Fig. 1A, panel c). We then used FACS analysis to examine the level of MHC-I expression on the cell surface. The peak with the highest relative intensity of fluorescence on the surface was observed with untreated BC-3 cells [Fig. 1B, BC-3 TPA(-)], but the peak shifted to low intensity with the TPA-treated BC-3 cells. The decrease of MHC-I on the cell surface of TPA-treated BC-3 cells was observed 6 h after treatment with TPA, and this decrease continued until 24 h in a kinetic fashion. When Ramos cells (a B-cell-derived cell-line used as a negative control) were treated with TPA, there was no shift of peak, as in the untreated sample (data not shown). These results indicated that some KSHV genes might be involved in down-regulation of MHC-I molecules. In order to identify a specific gene, we examined (by FACS analysis) HeLa cells that were transiently transfected with the K5 gene. The KSHV K5 gene fragment was amplified by PCR using primers with NheI and XhoI restriction sites at the 5' and 3' end respectively. The amplified fragment was digested with the enzyme, and then inserted into pcDNA3.1(+)/Zeo (Invitrogen) to create plasmid pcDNA3.1-K5. One day before transfection, HeLa cells (5x105) were seeded onto 60 mm dishes containing sterile glass coverslips and incubated at 37 °C in a 5% CO2 incubator. They were transfected with the expression plasmid, pcDNA3.1-K5, using SuperFect Transfection Reagent (Qiagen), according to the manufacturer’s instruction. HeLa cells were also transfected with a vector pcDNA3.1 as a negative control (HeLa-3.1 in Fig. 1B). At 24 h post-transfection, cells were washed with PBS, fixed with 2% paraformaldehyde for 20 min and permeabilized by 0·2% Triton-X 100 for 5 min; expression of K5 was then detected as described for IFA. When HeLa cells were stained with the MAb to K5 24 h after transfection, 60–70% of the cells expressed the K5 antigen (Fig. 1A, panel d), suggesting a relatively high transfection efficiency. Two peaks with low and high relative intensities of fluorescence were observed on the surface of HeLa-K5 cells, while only one peak, which had a high intensity of fluorescence, was observed on the untreated cells (Fig. 1B, right-hand panels). These findings indicated that the reduction of MHC-I expression on the cell surface was mediated by expression of the K5 gene and this effect was more prominent in the K5-transfected HeLa cells.
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). Second, we examined the effects of lytic replication of KSHV on the stability of MHC-I antigens. TPA-treated or untreated BC-3 cells were radiolabelled with 400 µCi/ml [35S]methionine for 15 min, and then chased for 30–120 min. After the chase period, the cells were lysed, incubated with anti-heavy chain antibody, and analysed on 15% SDS–PAGE as above. The results indicated that lytic replication of KSHV had no detectable effect on the stability of the MHC-I heavy chain (Fig. 2B). However, the density of a band from TPA-treated cells at 120 min chase was slightly fainter than that of the untreated sample (Fig. 2B). Coscoy & Ganem (2000) also reported that in pulse–chase experiments the half-life of MHC-I was reduced at later times in the presence of K5. Similar results were obtained in K5-expressing HeLa cells (data not shown). Then, we investigated the transport of MHC-I molecules in BC-3 cells treated with endo H. This enzyme cleaves immature, N-linked oligosaccharides residing in the ER and cis-Golgi – the more complex oligosaccharide forms in the medial-Golgi are resistant to endo H (Campbell & Slater, 1994 ). Lysates were prepared from BC-3 cells and immunoprecipitated with the anti-MHC-I MAb W6/32 as described above. The immunoprecipitates bound to protein G–Sepharose beads were divided into two equal aliquots in 50 mM potassium acetate buffer, pH 5·4, with 0·02% SDS and 0·1% NP-40, and heated to 95 °C for 5 min. After cooling on ice, 6 mU of endo H was added to one of the samples. Digestion was carried out for 8 h at 37 °C. The lysates were then fractionated by 10% denaturing SDS–PAGE and analysed by fluorography. The results shown in Fig. 2(C) demonstrate that MHC-I molecules in both untreated and treated BC-3 cells remained endo H-sensitive during the 15 min pulse-labelling and 30 min chase period, when compared with the samples that had not been exposed to endo H (compare lane 2 with 1; 4 with 3; 8 with 7; and 10 with 9) indicating that their location was inside the ER. However, after a 120 min chase, they acquired endo H resistance (Fig. 2C; compare lane 6 with 5, and 12 with 11), indicating their transport from the ER to the medial-Golgi. Identical results were demonstrated in K5-expressing HeLa cells (data not shown). Taken together, these results demonstrated that neither the lytic replication of KSHV nor the transfection of the K5 gene had a significant effect on the synthesis, stability or transport of MHC-I molecules.
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). As shown in Fig. 3, K5 antigens were clearly detectable in cells from PEL (Fig. 3A), endothelial cells (Fig. 3B) and spindle cells (Fig. 3C) of KS, and cells in MCD (Fig. 3D).
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). Some viral gene products prevent the transport of MHC-I peptides from the ER by interfering with this complex (Ahn et al., 1996 ; Burgert & Kvist, 1985 ; Jones et al., 1996 ). In KSHV-infected cells, MHC-I molecules were synthesized normally and were stable (Fig. 2
), suggesting that the K5 gene product does not prevent transport of MHC-I into the ER. Other possible mechanisms are that viral proteins bind to MHC-I molecules and retain them in the ER, and that viral proteins induce the retrograde-translocation of MHC-I molecules back into the cytosol. The E3/19K adenovirus 2 protein (Andersson et al., 1985 ; Burgert & Kvist, 1985 ) and the US3 protein of HCMV (Ahn et al., 1996 ; Jones et al., 1996 ) have been shown to bind directly to MHC-I heavy chains, thereby preventing their transport to the cell surface. HCMV US11 binds MHC-I molecules and redirects the MHC-I heavy chains to the cytosol (Wiertz et al., 1996 ). We were unable to detect such an association between the K5 protein and the MHC-I heavy chain by immunoprecipitation analysis of K5-transfected HeLa cells or TPA-induced BC-3 cells, using either anti-K5 or anti-MHC-I MAbs. This binding association was detected using a mild detergent, such as digitonin (Ahn et al., 1996 ; Jones et al., 1996 ). However, even using 1% digitonin, we were unable to detect such an association (data not shown). Glycosylated MHC-I molecules were not retained in the ER and were processed to molecules that were resistant to endo H treatment, suggesting that MHC-I molecules were transported to the Golgi apparatus from the ER. A final possible mechanism is internalization of MHC-I molecules from the cell surface. The HIV Nef protein modifies the endocytic machinery and thereby down-regulates surface expression of the MHC-I complex (Schwartz et al., 1996 ). K5-mediated down-regulation may be initiated by this mechanism, given that the MHC-I molecules were glycosylated and processed at least to the Golgi apparatus (Fig. 2C). Recently, similar results that support this idea have been reported (Ishido et al., 2000 ; Coscoy & Ganem, 2000 ). These experiments were done in K3- and K5-transfected cell lines, but neither group reported MHC-I down-regulation in latently KSHV-infected cell lines. In our experiments, in addition to a K5-expressing cell line, we also demonstrated down-regulation of MHC-I molecules in latently KSHV-infected cells after TPA treatment. It is interesting and important that such a phenomenon can be found in vivo. Results of immunohistochemical staining suggested that K5 antigen may be expressed in cells infected with KSHV during reactivation, and also may down-regulate MHC-I expression in vivo. In conclusion, we have demonstrated that the KSHV-encoded K5 protein down-regulates MHC-I molecules in KSHV-infected cells and have also detected expression of K5 antigen in vivo.
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Andersson, M., Paabo, S., Nilsson, T. & Peterson, P. A. (1985). Impaired intracellular transport of Class I MHC antigens as a possible means for adenovirus to evade immune surveillance. Cell 43, 215-222.[Medline]
Arvanitakis, L., Mesri, E. A., Nador, R. G., Said, J. W., Asch, A. S., Knowles, D. M. & Cesarman, E. (1996). Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi’s sarcoma-associated herpesvirus (KHSV/HHV-8) in the absence of Epstein–Barr virus. Blood 88, 2648-2654.
Burgert, H.-G. & Kvist, S. (1985). An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell 41, 987-997.[Medline]
Campbell, A. E. & Slater, J. S. (1994). Down-regulation of major histocompatibility complex class I synthesis by murine cytomegalovirus early gene expression. Journal of Virology 68, 1805-1811.
Cesarman, E., Chang, Y., Moore, P. S., Said, J. W. & Knowles, D. M. (1995). Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. New England Journal of Medicine 332, 1186-1191.
Coscoy, L. & Ganem, D. (2000). Kaposi’s sarcoma associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proceedings of the National Academy of Sciences, USA 97, 8051-8056.
Gao, S. J., Kingsley, L., Li, M., Zheng, W., Parravicini, C., Ziegler, J., Newton, R., Rinaldo, C. R., Saah, A., Phair, J., Detels, R., Chang, Y. & Moore, P. S. (1996). KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nature Medicine 2, 925-928.[Medline]
Haque, M., Chen, J., Ueda, K., Mori, Y., Nakano, K., Hirata, Y., Kanamori, S., Uchiyama, Y., Inagi, R., Okuno, T. & Yamanishi, K. (2000). Identification and analysis of the K5 gene of Kaposi’s sarcoma-associated herpesvirus. Journal of Virology 74, 2867-2875.
Ishido, S., Wang, C., Lee, B.-S., Cohen, G. B. & Jung, J. U. (2000). Downregulation of major histocompatibility complex class I molecules by Kaposi’s sarcoma-associated herpesvirus K3 and K5 proteins. Journal of Virology 74, 5300-5309.
Jennings, S. R., Rice, P. L., Kloszewski, E. D., Anderson, R. W., Thompson, D. L. & Tevethia, S. S. (1985). Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells. Journal of Virology 56, 757-766.
Jones, T. R., Wiertz, E. J. H. J., Fish, K. N., Nelson, J. A. & Ploegh, D. L. (1996). Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proceedings of the National Academy of Sciences, USA 93, 11327-11333.
Lehner, P. J., Karttunen, J. T., Wilkinson, G. W. G. & Cresswell, P. (1997). The human cytomegalovirus US6 glycoprotein inhibits transporter associated with antigen processing-dependent peptide translocation. Proceedings of the National Academy of Sciences, USA 94, 6904-6909.
Miller, G., Rigsby, M. O., Heston, L., Grogan, E., Sun, R., Metroka, C., Levy, J. A., Gao, S. J., Chang, Y. & Moore, P. (1996). Antibodies to butyrate-inducible antigens of Kaposi’s sarcoma-associated herpesvirus in patients with HIV-1 infection. New England Journal of Medicine 334, 1292-1297.
Miller, G., Heston, L., Grogan, E., Gradoville, L., Rigsby, M., Sun, R., Shedd, D., Kushnaryov, V. M., Grossberg, S. & Chang, Y. (1997). Selective switch between latency and lytic replication of Kaposi’s sarcoma herpesvirus and Epstein–Barr virus in dually infected body cavity lymphoma cells. Journal of Virology 71, 314-324.[Abstract]
Moore, P. S., Gao, S. J., Dominguez, G., Cesarman, E., Lungu, O., Knowles, D. M., Garber, R., McGeoch, D. J., Pellet, P. & Chang, Y. (1996). Primary characterization of a herpesvirus-like agent associated with Kaposi’s sarcoma. Journal of Virology 70, 549-558.[Abstract]
Parravicini, C., Chandran, B., Corbellino, M., Berti, E., Paulli, M., Moore, P. S. & Chang, Y. (2000). Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. American Journal of Pathology 156, 743-749.
Ploegh, H. L. (1998). Viral strategies of immune evasion. Science 280, 248-253.
Renne, R., Zhong, W., Herndier, B., McGrath, M., Abbey, N., Kedes, D. & Ganem, D. (1996). Lytic growth of Kaposi’s sarcoma associated herpesvirus (human herpesvirus 8) in culture. Nature Medicine 2, 342-346.[Medline]
Schwartz, O., Marechal, V., Gall, S. L., Lemonnier, F. & Heard, J.-M. (1996). Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nature Medicine 2, 338-342.[Medline]
Simpson, G. R., Schulz, T. F., Whitby, D., Cook, P. M., Boshoff, C., Rainbow, L., Howard, M. R., Gao, S. J., Bohenzky, R. A., Simmonds, P., Lee, C., de Ruiter, A., Hatzakis, A., Tedder, R. S., Weller, I. V., Weiss, R. A. & Moore, P. S. (1996). Prevalence of Kaposi’s associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348, 1133-1138.[Medline]
Soulier, J., Grollet, L., Oksenhendler, E., Cacoub, P., Cazalas-Hatem, D., Babinet, P., d’Agay, M. F., Clauvel, J. P., Raphael, M., Degos, L. & Sigaux, F. (1995). Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86, 1276-1280.
Wiertz, E. J. H. J., Jones, T. R., Sun, L., Bogyo, M., Geuze, H. J. & Ploegh, H. L. (1996). The human cytomegalovirus US 11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84, 769-779.[Medline]
Received 25 October 2000;
accepted 8 January 2001.
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