Expression pattern of asialoglycoprotein receptor in human testis

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.

Defined host factors support HBV infection in non‐hepatic 293T cells

“…Our engineered 293T cell model provides an alternative way to study HBV infection in other non‐hepatic cells. For example, when investigating HBV infection in spermatogonial cells, we can first examine the distribution of NTCP, HNF4α, RXRα and PPARα in human testis by multiple immunoenzyme histochemistry staining . Also, further application of this model will help to advance our knowledge of the hepatotropism of HBV and elucidate host and restriction factors responsible.…”

“…HBV genes can also be expressed in early embryonic cells originating from hamster oocytes fertilized with human spermatozoa transfected with the complete viral genome, and HBV infection can adversely affect human sperm due to HBV S protein‐mediated loss of sperm mitochondrial membrane potential, resulting in reduced sperm motility . However, we found that the asialoglycoprotein receptor (ASGR) was not expressed in human testis, suggesting that HBV might invade spermatogonial cells through other receptors . Although such restricted non‐hepatic infection of HBV has been observed, the host factors required for HBV infection in non‐hepatic cells remain only partially understood.…”

“…9 However, we found that the asialoglycoprotein receptor (ASGR) was not expressed in human testis, suggesting that HBV might invade spermatogonial cells through other receptors. 10 Although such restricted non-hepatic infection of HBV has been observed, the host factors required for HBV infection in non-hepatic cells remain only partially understood.…”

Molecular and structural changes related to hepatitis E virus antigen and its expression in testis inducing apoptosis in Mongolian gerbil model

“…Generally, the viruses enter into the testicles either via the blood, via lymphs or via the rete testis to establish the chronic viral infections that affect the sperm quality and subsequent male infertility . The presence of HIV, HBV or HCV in semen impairs sperm parameters and DNA integrity and particularly reduces forward motility . Furthermore, the virus‐infected semen has been associated with an increased frequency of sperm aneuploidy and DNA fragmentation .…”

“…18 The presence of HIV, HBV or HCV in semen impairs sperm parameters and DNA integrity and particularly reduces forward motility. 19,20 Furthermore, the virusinfected semen has been associated with an increased frequency of sperm aneuploidy and DNA fragmentation. 21 Several experimental infections with simian immune deficiency (SIV) and cytomegalovirus (CMV) showed testicular atrophy, necrotic seminiferous tubules and infiltrated neutrophils are relatively common findings in these infections.…”