Sex disparity in viral load, inflammation and liver damage in transgenic mice carrying full hepatitis B virus genome with the W4P mutation in the preS1 region.

Abstract

AIM:

To study sex disparity in susceptibility to hepatocellular carcinoma (HCC), we created a transgenic mouse model that expressed the full hepatitis B virus (HBV) genome with the W4P mutation.

METHODS:

Transgenic mice were generated by transferring the pHY92-1.1x-HBV-full genome plasmid (genotype A2) into C57Bl/6N mice. We compared serum levels of hepatitis B surface antigen (HBsAg), interleukin (IL)-6, and the liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), as well as liver histopathological features in male and female transgenic (W4P TG) mice and in nontransgenic littermates of 10 mo of age.

RESULTS:

W4P TG males exhibited more pronounced hepatomegaly, significantly increased granule generation in liver tissue, elevated HBsAg expression in the liver and serum, and higher serum ALT and IL-6 levels compared to W4P TG females or littermate control groups.

CONCLUSION:

Together, our data indicate that the W4P mutation in preS1 may contribute to sex disparity in susceptibility to HCC by causing increased HBV virion replication and enhanced IL-6-mediated inflammation in male individuals. Additionally, our transgenic mouse model that expresses full HBV genome with the W4P mutation in preS1 could be effectively used for the studies of the progression of liver diseases, including HCC.

• Authors: Seoung-Ae Lee, So-Young Lee, Yu-Min Choi, Hong Kim, Bum-Joon Kim
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 24 Issue 10 Pg. 1084-1092 (Mar 14 2018) ISSN: 2219-2840 [Electronic] United States
• PMID: 29563753 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Hepatitis B Surface Antigens
• Interleukin-6
• Protein Precursors
• interleukin-6, mouse
• presurface protein 1, hepatitis B surface antigen
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Carcinoma, Hepatocellular (blood, pathology, virology)
• Disease Susceptibility (blood, virology)
• Female
• Genome, Viral (genetics)
• Hepatitis B Surface Antigens (blood, genetics)
• Hepatitis B virus (genetics, isolation & purification)
• Hepatitis B, Chronic (blood, pathology, virology)
• Humans
• Interleukin-6 (blood)
• Liver (enzymology, pathology, virology)
• Liver Neoplasms (blood, pathology, virology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation
• Protein Precursors (blood, genetics)
• Sex Factors
• Viral Load