Mathematical modeling and analysis of virus-host interaction

2016 Fiscal Year Final Research Report

• Project Area: Molecular basis of host cell competency in virus infection
• Project/Area Number: 24115008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Graduate University for Advanced Studies
• Principal Investigator: Sasaki Akira 総合研究大学院大学, 先導科学研究科, 教授 (90211937)
• Co-Investigator(Kenkyū-buntansha): 小柳 義夫 京都大学, ウイルス研究所, 教授 (80215417)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: ウイルスと宿主の共進化 / ヒト化マウス / APOBEC / Vif / cell-to-cell感染 / マルチトロピズム / ネットワーク理論 / 時系列解析

Outline of Final Research Achievements

Coevolution of anti-retroviral protein APOBEC3G (A3G) of humans and its inhibitor Vif of HIV-1 is mathematically modeled, and revealed the the conditions with which coevolution ends up with equilibrium or indefinite escalation of their expression levels. Intra-host dynamics of viruses with multiple tropism is also analyzed with the framework of network dynamics, and its R0-centrality analysis revealed the optimum intervention strategy that typically recommends extremely focussed intervention to the most amplifying tissue.

Comparing the time series data of the infection experiments that excluded cell-to-cell infection of HIV-1 and those with both cell-to-cell and cell-free infections, we quantified their relative contributions to the basic reproductive number of viruses. Infection experiments using polymorphic HIV restriction factor A3H reveals the roles of A3H restriction + type and this counteracting Vif type have played in the coevolutionary dynamism between human and HIV-1.

Free Research Field

理論ウイルス学