arXiv subjects

J. Tomas Lazaro

Publications and source records attributed to J. Tomas Lazaro.

3 recordsLinked to original sources

arXiv2026

A mathematical model for fitness effects on viral persistence

Persistent viral infections arise from complex interactions between viral replication, host cell responses, and ongoing viral evolution. A general framework linking viral fitness to persistence dynamics is lacking. Here, we develop for the first time a mathematical model of viral persistence that takes into consideration viral fitness variations. Essential to the model is the partition of the classical fitness parameter into three components: replicative, infective, and dispersal fitness. The model was initially inspired by a new experiment on hepatitis C virus (HCV) persistence, established in human hepatoma cells, also reported in this work. This experiment documents two strikingly different viral trajectories depending on the initial replicative fitness of the viral population used to establish persistence. The dynamical model describes the interactions among uninfected cells, infected cells, and infectious virions, and it incorporates, through a continuum, two alternative mechanisms of viral release from cells: budding and lysis. Analysis of the model reveals that viral fitness parameters organise infection outcomes into distinct dynamical regimes. Low replicative and dispersal fitness values lead to viral extinction, whereas high values enable persistence through either stable coexistence or recurrent infection waves. The space of fitness discloses a hierarchy among these parameters, with replicative and dispersal fitness being able to trigger important shifts in the outcome of the infection as opposed to infective fitness. The model identifies trade-offs between replication and dispersal that shape viral production and predicts slow dynamical regimes in which infection may persist despite low detectable viral loads. It provide candidates mechanisms capable of generating the persistence patterns observed experimentally.

q-bio.PE↗

arXiv2024

Global bifurcation in a virus, defective genomes, satellite RNAs tripartite system: breakdown of a coexistence quasi-neutral curve

The dynamics of wild-type (wt) RNA viruses and their defective viral genomes (DVGs) have been extensively studied both experimentally and theoretically. This research has paid special attention to the interference effects of DVGs on wt accumulation, transmission, disease severity, and induction of immunological responses. This subject is currently a highly active. However, viral infections involving wt, DVGs and other subviral genetic elements, like viral RNA satellites (satRNAs) have received scarce attention. Satellites are molecular parasites genetically different from the wt virus, which exploit the products of the latter for their own replication in as much as DVGs do, and thus they need to coinfect host cells along with the wt virus to complete their replication cycle. Here, we analyze a mathematical model describing the initial replication phase of a wt virus producing DVGs and coinfecting with a satRNA. The model has three different dynamical regimes depending upon the wt replication rate ($α$), the fraction of DVGs produced during replication ($ω$), and the replication rate of the satRNA ($β$): ($i$) full extinction when $β> α(1 - ω)$; ($ii$) a bistable regime with full coexistence governed by a quasi-neutral curve of equilibria and full extinction when $β= α(1 - ω)$; and ($iii$) a scenario of bistability separating full extinction from wt-DVGs coexistence with no satRNA when $β< α(1 - ω)$. The transition from scenarios ($i$) to ($iii$) occurs through the creation and destruction of a quasi-neutral curve of equilibria in a global bifurcation that we name as \textit{quasi-neutral nullcline confluence} (QNC) bifurcation: at the bifurcation value, two nullcline hypersurfaces coincide, giving rise to the curve of equilibria.

q-bio.PE↗

arXiv2014

Dynamics and bifurcations in a simple quasispecies model of tumorigenesis

Cancer is a complex disease and thus is complicated to model. However, simple models that describe the main processes involved in tumoral dynamics, e.g., competition and mutation, can give us clues about cancer behaviour, at least qualitatively, also allowing us to make predictions. Here we analyze a simplified quasispecies mathematical model given by differential equations describing the time behaviour of tumor cells populations with different levels of genomic instability. We find the equilibrium points, also characterizing their stability and bifurcations focusing on replication and mutation rates. We identify a transcritical bifurcation at increasing mutation rates of the tumor cells population. Such a bifurcation involves an scenario with dominance of healthy cells and impairment of tumor populations. Finally, we characterize the transient times for this scenario, showing that a slight increase beyond the critical mutation rate may be enough to have a fast response towards the desired state (i.e., low tumor populations) during directed mutagenic therapies.

math.DS↗