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Molecular and structural changes related to Hepatitis E virus (HEV) antigen and its expression in testis inducing apoptosis in Mongolian gerbil model.

Molecular and structural changes related to Hepatitis E virus (HEV) antigen and its expression in testis inducing apoptosis in Mongolian gerbil model.
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Soomro MH, Shi R, She R, Yang Y, Wang T, Wu Q, Li H, Hao W,


Soomro MH, Shi R, She R, Yang Y, Wang T, Wu Q, Li H, Hao W, (click to view)

Soomro MH, Shi R, She R, Yang Y, Wang T, Wu Q, Li H, Hao W,

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Journal of viral hepatitis 2017 02 09() doi 10.1111/jvh.12690

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 day post inoculation and reached a peak between 28 to 42 days later with viral load between 3.12 logs g-¹ to 6.23 logs g-¹ by PCR assays. Microscopic changes showed vacuolation, sloughing of germ cells, formation of multinuclear giant cells, degeneration, necrosis of tubules and damaged blood-testis barrier was 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 was detectable through western blot. Lower (P<0.05) serum testosterone and higher (P<0.05) blood urea nitrogen (BUN) level was observed in inoculated Mongolian gerbils. Likewise, increased (P<0.05) germ cell apoptosis rate was detected with significant increased expression of Fas-L, Fas in HEV inoculated groups at each time points. Up-regulation (P < 0.05 or P < 0.01) in mRNA level of Fas-L, Fas, Bax, Bcl-2 and caspase-3 were seen 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. This article is protected by copyright. All rights reserved.

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