No specific drugs are currently available against hepatitis delta virus (HDV), a defective virus leading to the most severe form of chronic viral
hepatitis in man. The lack of convenient HDV
infection models has hampered the development of effective
therapeutics. In this study, naïve and hepatitis B virus (HBV) chronically infected humanized uPA/SCID mice were employed to establish a small animal model of HBV/HDV
coinfection and
superinfection. For preclinical
antiviral drug evaluation, the GMP version of the myristoylated preS-
peptide (
Myrcludex-B), a
lipopeptide derived from the pre-S1 domain of the HBV envelope, was applied to prevent de novo HBV/HDV
coinfection in vivo. Virological parameters were determined at serological and intrahepatic level both by real-time polymerase chain reaction (PCR) and by immunohistochemistry. Establishment of HDV
infection was highly efficient in both HBV-infected and naïve chimeric mice with HDV titers rising up to 1 × 10E9 copies/mL. Notably, HDV
superinfection led to a median 0.6log reduction of HBV
viremia, which although not statistically significant suggests that HDV may hinder HBV replication. In the setting of HBV/HDV simultaneous
infection, a majority of human hepatocytes stained
HDAg-positive long before HBV spreading was completed, confirming that HDV can replicate intrahepatically also in the absence of HBV
infection. Furthermore, the increase of HBV
viremia and intrahepatic cccDNA loads was significantly slower than in HBV mono-infected mice. Treatment with the HBV entry inhibitor
Myrcludex-B, efficiently hindered the establishment of HDV
infection in vivo.
CONCLUSION: