Abstract
During acute or chronic hepatitis B virus (HBV) infection, the virus can invade the male reproductive system, pass through the blood–testis barrier and integrate into the germ line, resulting in abnormal spermatozoa. However, the pathway remains unclear. The asialoglycoprotein receptor (ASGR), a potential receptor for HBV, is mainly distributed in hepatocytes. We have examined the distribution of ASGR in human testis and found it in the seminiferous tubules and interstitial region but its enrichment in human testis is much lower than that in liver. By multiple immunoenzyme histochemistry staining, ASGR was precisely co-localized with vimentin (Sertoli cell marker) but not proliferating cell nuclear antigen (spermatogonial cell marker) in testis tissue. ASGR was expressed in human Leydig cells, stromal cells in the seminiferous tubules and Sertoli cells but seldom in spermatogonial cells. Therefore, ASGR could provide HBV with access to the luminal compartment of human testis. The mechanism by which HBV invades germ cells remains unknown.
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References
Aumuller G, Steinbruck M, Krause W, Wagner HJ (1988) Distribution of vimentin-type intermediate filaments in Sertoli cells of the human testis, normal and pathologic. Anat Embryol (Berl) 178:129–136
Bar-Shira Maymon B, Yogev L, Yavetz H, Lifschitz-Mercer B, Schreiber L, Kleiman SE, Botchan A, Hauser R, Paz G (2003) Spermatogonial proliferation patterns in men with azoospermia of different etiologies. Fertil Steril 80:1175–1180
Benita Y, Cao Z, Giallourakis C, Li C, Gardet A, Xavier RJ (2010) Gene enrichment profiles reveal T-cell development, differentiation, and lineage-specific transcription factors including ZBTB25 as a novel NF-AT repressor. Blood 115:5376–5384
Cheng CY, Mruk DD (2012) The blood-testis barrier and its implications for male contraception. Pharmacol Rev 64:16–64
De Falco S, Ruvoletto MG, Verdoliva A, Ruvo M, Raucci A, Marino M, Senatore S, Cassani G, Alberti A, Pontisso P, Fassina G (2001) Cloning and expression of a novel hepatitis B virus-binding protein from HepG2 cells. J Biol Chem 276:36613–36623
Ganem D, Prince AM (2004) Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med 350:1118–1129
Glebe D, Gerlich WH (2004) Study of the endocytosis and intracellular localization of subviral particles of hepatitis B virus in primary hepatocytes. Methods Mol Med 96:143–151
Gong ZJ, De Meyer S, van Pelt J, Hertogs K, Depla E, Soumillion A, Fevery J, Yap SH (1999) Transfection of a rat hepatoma cell line with a construct expressing human liver annexin V confers susceptibility to hepatitis B virus infection. Hepatology 29:576–584
Hadchouel M, Scotto J, Huret JL, Molinie C, Villa E, Degos F, Brechot C (1985) Presence of HBV DNA in spermatozoa: a possible vertical transmission of HBV via the germ line. J Med Virol 16:61–66
Harvey HA, Jennings MP, Campbell CA, Williams R, Apicella MA (2001) Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol Microbiol 42:659–672
Henis YI, Katzir Z, Shia MA, Lodish HF (1990) Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing H1 and H2 polypeptides assessed by fluorescence photobleaching recovery. J Cell Biol 111:1409–1418
Hertogs K, Leenders WP, Depla E, De Bruin WC, Meheus L, Raymackers J, Moshage H, Yap SH (1993) Endonexin II, present on human liver plasma membranes, is a specific binding protein of small hepatitis B virus (HBV) envelope protein. Virology 197:549–557
Huang JM, Huang TH, Qiu HY, Fang XW, Zhuang TG, Qiu JW (2002) Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes. Asian J Androl 4:209–212
Huang JM, Huang TH, Qiu HY, Fang XW, Zhuang TG, Liu HX, Wang YH, Deng LZ, Qiu JW (2003) Effects of hepatitis B virus infection on human sperm chromosomes. World J Gastroenterol 9:736–740
Kang X, Xie Q, Zhou X, Li F, Huang J, Liu D, Huang T (2012) Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions. PLoS One 7:e33471
Lang ZW (1993) Distribution of hepatitis B virus in testicle tissue in patients with hepatitis B infection. Zhonghua Yi Xue Za Zhi 73:329–331
Mason A (2006) Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection. Minerva Gastroenterol Dietol 52:53–66
Mason A, Wick M, White H, Perrillo R (1993) Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection. Hepatology 18:781–789
Mason A, Theal J, Bain V, Adams E, Perrillo R (2005) Hepatitis B virus replication in damaged endothelial tissues of patients with extrahepatic disease. Am J Gastroenterol 100:972–976
Matthews CJ, Redfern CP, Hirst BH, Thomas EJ (1992) Characterization of human purified epithelial and stromal cells from endometrium and endometriosis in tissue culture. Fertil Steril 57:990–997
Mehdi H, Kaplan MJ, Anlar FY, Yang X, Bayer R, Sutherland K, Peeples ME (1994) Hepatitis B virus surface antigen binds to apolipoprotein H. J Virol 68:2415–2424
Moretti E, Federico MG, Giannerini V, Collodel G (2008) Sperm ultrastructure and meiotic segregation in a group of patients with chronic hepatitis B and C. Andrologia 40:286–291
Neurath AR, Strick N (1990) Antigenic mimicry of an immunoglobulin A epitope by a hepatitis B virus cell attachment site. Virology 178:631–634
Owada T, Matsubayashi K, Sakata H, Ihara H, Sato S, Ikebuchi K, Kato T, Azuma H, Ikeda H (2006) Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry. J Viral Hepat 13:11–18
Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD (2003) Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 77:546–559
Scott RM, Snitbhan R, Bancroft WH, Alter HJ, Tingpalapong M (1980) Experimental transmission of hepatitis B virus by semen and saliva. J Infect Dis 142:67–71
Treichel U, Meyer zum Buschenfelde KH, Stockert RJ, Poralla T, Gerken G (1994) The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. J Gen Virol 75:3021–3029
Treichel U, Meyer zum Buschenfelde KH, Dienes HP, Gerken G (1997) Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol 142:493–498
van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, Kuiken T (2006) H5N1 virus attachment to lower respiratory tract. Science 312:399
Wang P, Wang X, Cong S, Ma H, Zhang X (2008) Mutation analyses of integrated HBV genome in hepatitis B patients. J Genet Genomics 35:85–90
Zhou XL, Sun PN, Huang TH, Xie QD, Kang XJ, Liu LM (2009) Effects of hepatitis B virus S protein on human sperm function. Hum Reprod 24:1575–1583
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This work was supported by the National Nature Science Foundation of China (no. 30901609, no. 30801241) and the China Postdoctoral Science Foundation (no. 200902333).
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Sun, P., Zheng, J., She, G. et al. Expression pattern of asialoglycoprotein receptor in human testis. Cell Tissue Res 352, 761–768 (2013). https://doi.org/10.1007/s00441-013-1616-8
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DOI: https://doi.org/10.1007/s00441-013-1616-8