Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers

• DOI: 10.1371/journal.pcbi.1011238
• Publication Date: 2024-03-11T17:42:31Z
• Authors: Kosaku Kitagawa; Kwang Su Kim; Masashi Iwamoto; Sanae Hayashi; Hyeongki Park; Takara Nishiyama; Naotoshi Nakamura; Yasuhisa Fujita; Shinji Nakaoka; Kazuyuki Aihara; Alan S. Perelson; Lena Allweiss; Maura Dandri; Koichi Watashi; Yasuhito Tanaka; Shingo Iwami
• Keywords: cccDNA; Hepatitis B; HBeAg

Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in nucleus infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating cccDNA remains challenging. Thus, quantifying and understanding dynamics are essential for developing effective treatment strategies new drugs. However, such study requires repeated liver biopsy to measure intrahepatic cccDNA, which basically not accepted because potentially morbid common during treatment. We here aimed develop a noninvasive method using surrogate markers peripheral blood. constructed multiscale mathematical model that explicitly incorporates both intracellular intercellular HBV processes. The model, based on age-structured partial differential equations, integrates experimental data from vitro vivo investigations. By applying this we roughly predicted amount within certain range specific viral serum samples, including DNA, HBsAg, HBeAg, HBcrAg. Our represents significant step towards advancing chronic infection. quantification our proposed holds promise improving clinical analyses strategies. comprehensively describing interactions all components involved infection, provides valuable framework further research development targeted interventions.