Early Multiphasic HBV Infection Initiation Kinetics Is Not Clone-Specific and Is Not Affected by Hepatitis D Virus (HDV) Infection
The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA
Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan
Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima 734-8551, Japan
Liver Diseases Branch, NIDDK, NIH, Bethesda, MD 20892, USA
PhoenixBio Co., Ltd., Higashi-Hiroshima, Hiroshima 739-0046, Japan
Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 263; https://doi.org/10.3390/v11030263
Received: 11 February 2019 / Revised: 8 March 2019 / Accepted: 13 March 2019 / Published: 15 March 2019
(This article belongs to the Section Animal Viruses)
Backgrounds and Aims: We previously demonstrated that serum hepatitis B virus (HBV) DNA in HBV infected humanized mice exhibited a highly dynamic multiphasic kinetic pattern from infection initiation to steady-state. Here, we investigated whether this pattern is consistent across different HBV clones or in the presence of hepatitis D virus (HDV) co-infection. Methods: We analyzed early serum viral kinetics using 26 HBV genotype C (GtC) mono-infected mice [clones: PXB, Hiroshima GtC CL4 (CL4) and Hiroshima GtC CL5 (CL5)] and four HBV CL4/HDV genotype one co-infected mice. Results: The HBV kinetics observed with clones CL4 and CL5 were similar to that previously defined in HBV PXB infected mice. Additionally, no significant differences in HBV DNA levels were observed between HBV mono-infected and HBV/HDV co-infected mice through 4 weeks post-inoculation (p.i.). However, HBV DNA levels at 6 weeks p.i. in HBV/HDV co-infected mice were significantly lower than those in HBV mono-infected mice (P = 0.002), consistent with HDV suppression of chronic HBV. Conclusions: HBV infection initiation is multiphasic across multiple viral clones and is not altered by HDV co-infection. The latter suggests that higher HDV titers (>8 log IU/mL) and/or longer duration of HDV infection might be needed to trigger HDV-induced suppression on HBV.