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      Lyapunov function and global asymptotic stability for a new multiscale viral dynamics model incorporating the immune system response: Implemented upon HCV

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          Abstract

          In this paper, a new mathematical model is formulated that describes the interaction between uninfected cells, infected cells, viruses, intracellular viral RNA, Cytotoxic T-lymphocytes (CTLs), and antibodies. Hence, the model contains certain biological relations that are thought to be key factors driving this interaction which allow us to obtain precise logical conclusions. Therefore, it improves our perception, that would otherwise not be possible, to comprehend the pathogenesis, to interpret clinical data, to control treatment, and to suggest new relations. This model can be used to study viral dynamics in patients for a wide range of infectious diseases like HIV, HPV, HBV, HCV, and Covid-19. Though, analysis of a new multiscale HCV model incorporating the immune system response is considered in detail, the analysis and results can be applied for all other viruses. The model utilizes a transformed multiscale model in the form of ordinary differential equations (ODE) and incorporates into it the interaction of the immune system. The role of CTLs and the role of antibody responses are investigated. The positivity of the solutions is proven, the basic reproduction number is obtained, and the equilibrium points are specified. The stability at the equilibrium points is analyzed based on the Lyapunov invariance principle. By using appropriate Lyapunov functions, the uninfected equilibrium point is proven to be globally asymptotically stable when the reproduction number is less than one and unstable otherwise. Global stability of the infected equilibrium points is considered, and it has been found that each equilibrium point has a specific domain of stability. Stability regions could be overlapped and a bistable equilibria could be found, which means the coexistence of two stable equilibrium points. Hence, the solution converges to one of them depending on the initial conditions.

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          Most cited references43

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          Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission.

          A precise definition of the basic reproduction number, R0, is presented for a general compartmental disease transmission model based on a system of ordinary differential equations. It is shown that, if R0 1, then it is unstable. Thus, R0 is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for R0 near one. This criterion, together with the definition of R0, is illustrated by treatment, multigroup, staged progression, multistrain and vector-host models and can be applied to more complex models. The results are significant for disease control.
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            On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations.

            The expected number of secondary cases produced by a typical infected individual during its entire period of infectiousness in a completely susceptible population is mathematically defined as the dominant eigenvalue of a positive linear operator. It is shown that in certain special cases one can easily compute or estimate this eigenvalue. Several examples involving various structuring variables like age, sexual disposition and activity are presented.
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              HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

              A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t 1/2 = 1.6 days), and plasma virions were estimated to have a mean life-span of 0.3 days (t 1/2 = 0.24 days). The estimated average total HIV-1 production was 10.3 x 10(9) virions per day, which is substantially greater than previous minimum estimates. The results also suggest that the minimum duration of the HIV-1 life cycle in vivo is 1.2 days on average, and that the average HIV-1 generation time--defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles--is 2.6 days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also theoretical principles to guide the development of treatment strategies.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 October 2021
                2021
                : 16
                : 10
                : e0257975
                Affiliations
                [1 ] Faculty of Engineering, Department of Engineering Mathematics and Physics, Alexandria University, Alexandria, Egypt
                [2 ] High Institute of Public Health, Alexandria University, Alexandria, Egypt
                National Institute of Infectious Diseases, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-0616-1732
                https://orcid.org/0000-0002-5013-3157
                Article
                PONE-D-21-12161
                10.1371/journal.pone.0257975
                8509987
                34637445
                7e441e84-ae97-44e6-aade-5043b0ef6987
                © 2021 Elkaranshawy et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 April 2021
                : 14 September 2021
                Page count
                Figures: 14, Tables: 2, Pages: 26
                Funding
                The author(s) received no specific funding for this work.
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                Biology and Life Sciences
                Immunology
                Immune Response
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                Immune Physiology
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