Abstract Viruses proliferate through both genome replication inside infected cells and transmission to new target cells or to new hosts. Each viral genome molecule in infected cells is used either for amplifying the intracellular genome as a template (“stay-at-home strategy”) or for packaging into progeny virions to be released extracellularly (“leaving-home strategy”). The balance between these strategies is important for both initial growth and transmission of viruses. In this study, we used hepatitis C virus (HCV) as a model system to study the functions of viral genomic RNA in both RNA replication in cells and in progeny virus assembly and release. Using viral infection assays combined with mathematical modelling, we characterized the dynamics of two different HCV strains (JFH-1, a clinical isolate, and Jc1-n, a laboratory strain), which have different viral assembly and release characteristics. We found that 1.27% and 3.28% of JFH-1 and Jc1-n intracellular viral RNAs, respectively, are used for producing and releasing progeny virions. Analysis of the Malthusian parameter of the HCV genome (i.e., initial growth rate) and the number of de novo infections (i.e., initial transmissibility) suggests that the leaving-home strategy provides a higher level of initial transmission for Jc1-n, while, in contrast, the stay-at-home strategy provides a higher initial growth rate for JFH-1. Thus, theoretical-experimental analysis of viral dynamics enables us to better understand the proliferation strategies of viruses. Ours is the first study to analyze stay-leave trade-offs during the viral life cycle and their significance for viral proliferation.
Abstract Among the four groups of HIV-1 (M, N, O and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing ‘intrinsic herd immunity’, whereas Vpu has evolved in HIV-1M as a tetherin antagonist.
Citation: Toshikazu Kuniya, Hisashi Inaba. Possible effects of mixed prevention strategy for COVID-19 epidemic: massive testing, quarantine and social distancing[J]. AIMS Public Health, 2020, 7(3): 490-503. doi: 10.3934/publichealth.2020040
In this paper, we consider a mathematical model for the spread of a directly transmitted infectious disease in an age-structured population.We assume that infected population is recovered with permanent immunity or quarantined by an age-specific schedule, and the infective agentcan be transmitted not only horizontally but also vertically from adult individuals to their newborns. For simplicity we assume that thedemographic process of the host population is not affected by the spread of the disease, hence the host population is a demographic stable population.First we establish the mathematical well-posedness of the time evolution problem by using the semigroup approach. Next we prove that the basicreproduction ratio is given as the spectral radius of a positive operator, and an endemic steady state exists if and only if the basic reproductionratio $R_0$ is greater than unity, while the disease-free steady state is globally asymptotically stable if $R_0 < 1$. We also show that the endemicsteady states are forwardly bifurcated from the disease-free steady state when $R_0$ crosses the unity. Finally we examine the conditions for the localstability of the endemic steady states.
Effects of age shift on the tempo and quantum of non-repeatable demographic events are examined. The purpose is to develop a period index theory based on the survival model and to provide a mathematically consistent interpretation of Bongaarts and Feeney's tempo adjustment arguments. The survival model for non-repeatable events is introduced. In the time-inhomogeneous case, three types of period survival models are considered. McKendrick equation is used to formulate the risk population dynamics. The tempo and quantum indices for three period survival models are computed when the period age shift occurs for the hazard, the incidence, and the survival rates. Bongaarts and Feeney's tempo adjustment arguments are consistently based on the scenario of the period age shift on the survival rate, and they give translation formulae between period indices without referring to cohort. Traditional demographic translation formulae between cohort and period indices are reviewed to clarify differences between cohort- and period-oriented translation procedures.
