Previous Article | Next Article 
J Virol, August 1998, p. 6621-6628, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Human Homolog of HAVcr-1 Codes for a Hepatitis
A Virus Cellular Receptor
Dino
Feigelstock,
Peter
Thompson,
Pravina
Mattoo,
Yuan
Zhang, and
Gerardo G.
Kaplan*
Laboratory of Hepatitis Viruses, Division of
Viral Products, Center for Biologics Evaluation and Research, Food
and Drug Administration, Bethesda, Maryland 20892
Received 12 March 1998/Accepted 13 May 1998
The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA was
isolated from a cDNA expression library of African green monkey kidney
(AGMK) cells by using protective monoclonal antibody (MAb) 190/4, which
blocks the binding of hepatitis A virus (HAV) to AGMK cells. The
HAVcr-1 cDNA codes for havcr-1, a 451-amino-acid class I
integral-membrane mucin-like glycoprotein of unknown natural function.
To determine the existence of a human homolog(s) of HAVcr-1
(huHAVcr-1), we used HAVcr-1-specific primers to amplify cDNAs
from human liver and kidney mRNA by reverse transcription-PCR. Nucleotide sequence analysis revealed that the amplified liver and
kidney huHAVcr-1 cDNAs were identical and that they coded for a
359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79% identical to havcr-1. The six Cys residues of the extracellular domain of havcr-1 and its first
N-glycosylation site were conserved in huhavcr-1. However, the
number of hexameric repeats of the mucin-like region was
reduced from 27 in havcr-1 to 13 in huhavcr-1. In addition, 12 C-terminal amino acids in the cytoplasmic domain of huhavcr-1 were
deleted. Northern blot analysis of poly(A) RNA showed that
huhavcr-1 is expressed in every organ analyzed, including the liver,
small intestine, colon, and spleen, and that it is
expressed at higher levels in the kidney and testis. Although dog
cells transfected with the huHAVcr-1 cDNA did not express the
protective 190/4 epitope, they bound hepatitis A virus (HAV) and gained
limited susceptibility to HAV infection. Treatment with MAb 190/4 did
not protect AGMK cell transfectants expressing huhavcr-1 against HAV,
suggesting that HAV infected these cells via the huhavcr-1 receptor
and not the endogenously expressed havcr-1, which was blocked by MAb
190/4. Our data demonstrate that huhavcr-1 is a binding receptor for HAV and suggest that it is also a functional receptor for HAV.
*
Corresponding author. Mailing address: Division of
Viral Products, CBER-FDA, 8800 Rockville Pike, Bldg. 29A-NIH, rm. no.
1D10, HFM-448, Bethesda, MD 20892. Phone: (301) 827-1870. Fax: (301) 480-5326. E-mail: gk{at}helix.nih.gov.
J Virol, August 1998, p. 6621-6628, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Snooks, M. J., Bhat, P., Mackenzie, J., Counihan, N. A., Vaughan, N., Anderson, D. A.
(2008). Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes. J. Virol.
82: 8733-8742
[Abstract]
[Full Text]
-
Zhou, Y., Vaidya, V. S., Brown, R. P., Zhang, J., Rosenzweig, B. A., Thompson, K. L., Miller, T. J., Bonventre, J. V., Goering, P. L.
(2008). Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium. Toxicol Sci
101: 159-170
[Abstract]
[Full Text]
-
Xiao, S., Najafian, N., Reddy, J., Albin, M., Zhu, C., Jensen, E., Imitola, J., Korn, T., Anderson, A. C., Zhang, Z., Gutierrez, C., Moll, T., Sobel, R. A., Umetsu, D. T., Yagita, H., Akiba, H., Strom, T., Sayegh, M. H., DeKruyff, R. H., Khoury, S. J., Kuchroo, V. K.
(2007). Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function. JEM
204: 1691-1702
[Abstract]
[Full Text]
-
Wilker, P. R., Sedy, J. R., Grigura, V., Murphy, T. L., Murphy, K. M.
(2007). Evidence for carbohydrate recognition and homotypic and heterotypic binding by the TIM family. Int Immunol
19: 763-773
[Abstract]
[Full Text]
-
Tami, C., Silberstein, E., Manangeeswaran, M., Freeman, G. J., Umetsu, S. E., DeKruyff, R. H., Umetsu, D. T., Kaplan, G. G.
(2007). Immunoglobulin A (IgA) Is a Natural Ligand of Hepatitis A Virus Cellular Receptor 1 (HAVCR1), and the Association of IgA with HAVCR1 Enhances Virus-Receptor Interactions. J. Virol.
81: 3437-3446
[Abstract]
[Full Text]
-
van Timmeren, M. M., Bakker, S. J. L., Vaidya, V. S., Bailly, V., Schuurs, T. A., Damman, J., Stegeman, C. A., Bonventre, J. V., van Goor, H.
(2006). Tubular kidney injury molecule-1 in protein-overload nephropathy. Am. J. Physiol. Renal Physiol.
291: F456-F464
[Abstract]
[Full Text]
-
Larson, J. H., Kumar, C. G., Everts, R. E., Green, C. A., Everts-van der Wind, A., Band, M. R., Lewin, H. A.
(2006). Discovery of eight novel divergent homologs expressed in cattle placenta. Physiol. Genomics
25: 405-413
[Abstract]
[Full Text]
-
Konduru, K., Kaplan, G. G.
(2006). Stable Growth of Wild-Type Hepatitis A Virus in Cell Culture. J. Virol.
80: 1352-1360
[Abstract]
[Full Text]
-
Chen, T. T., Li, L., Chung, D.-H., Allen, C. D.C., Torti, S. V., Torti, F. M., Cyster, J. G., Chen, C.-Y., Brodsky, F. M., Niemi, E. C., Nakamura, M. C., Seaman, W. E., Daws, M. R.
(2005). TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. JEM
202: 955-965
[Abstract]
[Full Text]
-
Chakravarti, S., Sabatos, C. A., Xiao, S., Illes, Z., Cha, E. K., Sobel, R. A., Zheng, X. X., Strom, T. B., Kuchroo, V. K.
(2005). Tim-2 regulates T helper type 2 responses and autoimmunity. JEM
202: 437-444
[Abstract]
[Full Text]
-
Han, W. K., Alinani, A., Wu, C.-L., Michaelson, D., Loda, M., McGovern, F. J., Thadhani, R., Bonventre, J. V.
(2005). Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma. J. Am. Soc. Nephrol.
16: 1126-1134
[Abstract]
[Full Text]
-
Feigelstock, D. A., Thompson, P., Kaplan, G. G.
(2005). Growth of Hepatitis A Virus in a Mouse Liver Cell Line. J. Virol.
79: 2950-2955
[Abstract]
[Full Text]
-
Sanchez, G., Aragones, L., Costafreda, M. I., Ribes, E., Bosch, A., Pinto, R. M.
(2004). Capsid Region Involved in Hepatitis A Virus Binding to Glycophorin A of the Erythrocyte Membrane. J. Virol.
78: 9807-9813
[Abstract]
[Full Text]
-
Khademi, M., Illes, Z., Gielen, A. W., Marta, M., Takazawa, N., Baecher-Allan, C., Brundin, L., Hannerz, J., Martin, C., Harris, R. A., Hafler, D. A., Kuchroo, V. K., Olsson, T., Piehl, F., Wallstrom, E.
(2004). T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis. J. Immunol.
172: 7169-7176
[Abstract]
[Full Text]
-
Silberstein, E., Xing, L., van de Beek, W., Lu, J., Cheng, H., Kaplan, G. G.
(2003). Alteration of Hepatitis A Virus (HAV) Particles by a Soluble Form of HAV Cellular Receptor 1 Containing the Immunoglobulin- and Mucin-Like Regions. J. Virol.
77: 8765-8774
[Abstract]
[Full Text]
-
Bailly, V., Zhang, Z., Meier, W., Cate, R., Sanicola, M., Bonventre, J. V.
(2002). Shedding of Kidney Injury Molecule-1, a Putative Adhesion Protein Involved in Renal Regeneration. J. Biol. Chem.
277: 39739-39748
[Abstract]
[Full Text]
-
Dotzauer, A., Gebhardt, U., Bieback, K., Göttke, U., Kracke, A., Mages, J., Lemon, S. M., Vallbracht, A.
(2000). Hepatitis A Virus-Specific Immunoglobulin A Mediates Infection of Hepatocytes with Hepatitis A Virus via the Asialoglycoprotein Receptor. J. Virol.
74: 10950-10957
[Abstract]
[Full Text]
-
Blank, C. A., Anderson, D. A., Beard, M., Lemon, S. M.
(2000). Infection of Polarized Cultures of Human Intestinal Epithelial Cells with Hepatitis A Virus: Vectorial Release of Progeny Virions through Apical Cellular Membranes. J. Virol.
74: 6476-6484
[Abstract]
[Full Text]
-
Schneider-Schaulies, J.
(2000). Cellular receptors for viruses: links to tropism and pathogenesis. J. Gen. Virol.
81: 1413-1429
[Full Text]