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Androgens Promote Hepatitis B Virus Replication, Helping Explain Sex Differences

The hepatitis B virus (HBV) carries receptors for androgens -- male hormones such as testosterone -- which may help explain why men are more likely than women to develop chronic hepatitis B and experience more aggressive liver disease, according to study findings reported in the February 2012 Journal of Virology.

In an effort to understand why HBV chronically infects more men than women, Yongjun Tian and James Ou from the Keck School of Medicine at the University of Southern California and colleagues analyzed viral replication in mouse models, looking at transgenic mice genetically engineered to carry the HBV genome, with or without the ability to express the HBV X protein (HBx).

Results

• Sex of the mice had effect on HBV surface antigen (HBsAg), HBV DNA, or HBV RNA levels before puberty.
• After puberty -- when sex hormones reach different levels in males and females -- HBV replicated approximately twice as efficiently in male mice compared with females, whether or not HBx was expressed.
• Removing the testicles of male mice led to a reduction of HBV HBsAg, HBV DNA, and HBV RNA levels, but these could be partially restored by injecting an androgen agonist (R1881).
• Further studies revealed that the effect of androgen on HBV was dependent on its receptor on cells, "which apparently could also stimulate HBV replication via an androgen-independent pathway."
• 2 previously identified androgen response elements in the HBV genome mediated the effect of androgen on HBV RNA transcription and DNA replication.

"Our studies allowed us to understand the gender disparity of HBV carriers, and why this virus tends to cause more severe liver disease in men than in women," Ou said in a media advisory issued by the American Society For Microbiology, which publishes the journal.

Epidemiologic studies have shown that men are 3 to 7 times more likely than women to become HBV carriers, and male carriers are more likely to develop hepatocellular carcinoma, the researchers noted in their discussion.

"It remains to be determined, however, why HBV has evolved this mechanism to enhance its replication in males," they continued. "It is possible that a higher replication level in men will facilitate the horizontal transmission of this virus, whereas a lower replication level in women may facilitate the establishment of persistent infection after vertical transmission. The latter is supported by our recent finding that low-level HBV infection allows HBV to use the interferon response to enhance its replication and persistence."

Investigator affiliations: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA.

2/21/12

Reference

Y Tian, CF Kuo, WL Chen, and JH Ou. Enhancementof hepatitis B virus replication by androgen and its receptor in mice. Journal of Virology 86(4):1904-1910. February 2012.

Other Source

American Society For Microbiology. Androgen Boosts Hepatitis B Virus Replication. Media advisory. February 15, 2012.