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

Abstract

Hepatitis E virus (HEV) infection has been associated with a wide range of extrahepatic manifestations, so this study was designed to examine the effect and role of HEV on structural and molecular changes in the testicular tissues of Mongolian gerbils experimentally infected with swine HEV. HEV RNA was first detected in testis at 14 days post-inoculation and reached a peak between 28 and 42 days later with viral load between 3.12 and 6.23 logs/g by PCR assays. Changes including vacuolation, sloughing of germ cells, formation of multinuclear giant cells, degeneration, necrosis of tubules and damaged blood-testis barrier were observed through transmission electron microscopy. HEV ORF2 antigen was detected in the sperm cell cytoplasm along with decrease in relative protein of zonula occludens-1 through immunohistochemistry. HEV ORF3 antigen and ZO-1 protein were detectable by Western blotting. Lower (P<.05) serum testosterone and higher (P<.05) blood urea nitrogen level was observed in inoculated Mongolian gerbils. Likewise, increased (P<.05) germ cell apoptosis rate was detected with significant increased expression of Fas-L and Fas in HEV-inoculated groups at each time points. Up-regulation (P<.05 or P<.01) in mRNA level of Fas-L, Fas, Bax, Bcl-2 and caspase-3 was observed in HEV RNA-positive testes. Our study demonstrated that after experimental inoculation, HEV can be detected in testis tissues and viral proteins produce structural and molecular changes that in turn disrupt the blood-testis barrier and induce germ cell apoptosis.

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

“…The pathogenesis of HEV in the genital system is not largely understood. HEV-4 could disrupt the blood-testis barrier in the Mongolian gerbils' model and BALB/c mice, inducing the necrosis of tubules, germ cell apoptosis, and testicular damage [22,32]. In addition, HEV RNA was detected in pig semen in Shaanxi Province, China, and the semen of infertile males [23,33].…”

Effect of liver fibrotic changes on testicular histological structure: An updated review

“…They reported that HEV itself does not damage the tissues or site; it is the immune system that results in these histopathological alternations in the infected tissues [41]. In chronic cholestatic liver dysfunction model induced by bile duct ligation in mice and chickens, testes showed many structural changes including tubular distortion and atrophy, associated with thick irregular boundaries, vacuolation, disorganized epithelium, and exfoliated cells [42,43]. These changes were reported to result from "the detergent-like effect of the toxic bile acids" which is known to enhance membranous lipid polarity and fluidity [44,45].…”

Fighting Cancer with Mathematics and Viruses

“…These models only allowed budding as a mechanism for viral particle production from syncytia, assuming that no apoptosis occurs from fused cells [ 158 ]. Recent reports suggest that this may not be the case [ 159 , 160 , 161 , 162 , 163 , 164 , 165 ], depending on the virus; adjustments during model development and fitting can resolve such issues. In their model, Jacobsen and Pilyugin found that an increase in burst size would allow for tumor control.…”