Influenza A virus infection kinetics: quantitative data and models

Smith, Amber M.; Perelson, Alan S.

doi:10.1002/wsbm.129

Cited by 153 publications

(201 citation statements)

References 104 publications

(454 reference statements)

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“…This simple model and variants have been used in several recent analyses of influenza A virus within-host infection dynamics (e.g. [35,36] for reviews). The model tracks uninfected cells, U; infected cells, I; and free infectious virus, V. Cells become infected at rate k, infected cells produce virus at rate p and die at rate d. Free virus is cleared at rate d. The equations for uninfected cells, infected cells and free virus are given by dU/dt ¼ 2kUV, dI/dt ¼ 2kUV2dI and dV/dt ¼ pI2dV.…”

Section: Materials and Methods (A) Experimental Datamentioning

confidence: 99%

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

et al. 2014

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Trade-offs between different components of a pathogen's replication and transmission cycle are thought to be common. A number of studies have identified trade-offs that emerge across scales, reflecting the tension between strategies that optimize within-host proliferation and large-scale population spread. Most of these studies are theoretical in nature, with direct experimental tests of such cross-scale trade-offs still rare. Here, we report an analysis of avian influenza A viruses across scales, focusing on the phenotype of temperaturedependent viral persistence. Taking advantage of a unique dataset that reports both environmental virus decay rates and strain-specific viral kinetics from duck challenge experiments, we show that the temperature-dependent environmental decay rate of a strain does not impact within-host virus load. Hence, for this phenotype, the scales of within-host infection dynamics and between-host environmental persistence do not seem to interact: viral fitness may be optimized on each scale without cross-scale trade-offs. Instead, we confirm the existence of a temperature-dependent persistence trade-off on a single scale, with some strains favouring environmental persistence in water at low temperatures while others reduce sensitivity to increasing temperatures. We show that this temperature-dependent trade-off is a robust phenomenon and does not depend on the details of data analysis. Our findings suggest that viruses might employ different environmental persistence strategies, which facilitates the coexistence of diverse strains in ecological niches. We conclude that a better understanding of the transmission and evolutionary dynamics of influenza A viruses probably requires empirical information regarding both within-host dynamics and environmental traits, integrated within a combined ecological and within-host framework.

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Section: Materials and Methods (A) Experimental Datamentioning

confidence: 99%

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

et al. 2014

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“…Accordingly, elevated cell surface NA protein expression would decrease this length of time. Although our and other models of influenza virus fitness do not take into account the eclipse phase of viral growth, it is evident that variations in NA protein expression impact viral fitness for multiple subtypes of influenza viruses, and an altered eclipse phase is one potential mechanism of such changes (79). Further studies in the NHBE cell model will be required to properly determine these kinetic parameters of influenza B virus replication.…”

Section: Discussionmentioning

confidence: 99%

Competitive Fitness of Influenza B Viruses with Neuraminidase Inhibitor-Resistant Substitutions in a Coinfection Model of the Human Airway Epithelium

Burnham

Armstrong

Webster

et al. 2015

J Virol

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Influenza A and B viruses are human pathogens that are regarded to cause almost equally significant disease burdens. Neuraminidase (NA) inhibitors (NAIs) are the only class of drugs available to treat influenza A and B virus infections, so the development of NAI-resistant viruses with superior fitness is a public health concern. The fitness of NAI-resistant influenza B viruses has not been widely studied. Here we examined the replicative capacity and relative fitness in normal human bronchial epithelial (NHBE) cells of recombinant influenza B/Yamanashi/166/1998 viruses containing a single amino acid substitution in NA generated by reverse genetics (rg) that is associated with NAI resistance. The replication in NHBE cells of viruses with reduced inhibition by oseltamivir (recombinant virus with the E119A mutation generated by reverse genetics [rg-E119A], rg-D198E, rg-I222T, rg-H274Y, rg-N294S, and rg-R371K, N2 numbering) or zanamivir (rg-E119A and rg-R371K) failed to be inhibited by the presence of the respective NAI. In a fluorescence-based assay, detection of rg-E119A was easily masked by the presence of NAI-susceptible virus. We coinfected NHBE cells with NAI-susceptible and -resistant viruses and used next-generation deep sequencing to reveal the order of relative fitness compared to that of recombinant wild-type (WT) virus generated by reverse genetics (rg-WT): rg-H274Y > rg-WT > rg-I222T > rg-N294S > rg-D198E > rg-E119A Ͼ Ͼ rg-R371K. Based on the lack of attenuated replication of rg-E119A in NHBE cells in the presence of oseltamivir or zanamivir and the fitness advantage of rg-H274Y over rg-WT, we emphasize the importance of these substitutions in the NA glycoprotein. Human infections with influenza B viruses carrying the E119A or H274Y substitution could limit the therapeutic options for those infected; the emergence of such viruses should be closely monitored. Annual vaccination is an effective method for controlling influenza disease. The current FDA-approved quadrivalent seasonal influenza vaccine includes both antigenically distinct hemagglutinin (HA) lineages of influenza B virus (i.e., Yamagata and Victoria) (8, 9). Antiviral treatment is another option for the control of influenza, and the neuraminidase (NA) inhibitors (NAIs) are currently the only class of antivirals approved for prophylaxis and treatment of influenza B virus infections. NAIs limit influenza

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“…Thus, mathematical modeling has been used to capture the dynamics of influenza virus infection and to understand the interaction of the virus with the immune system (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Much of the work has been focused on the basic relationship between the host and the virus (25,26,32,34,35), whereas other work has strived to quantify the interplay between viral replication and adaptive immunity (27)(28)(29)(30)36). These models have been important to estimate the kinetic parameters describing influenza virus infection (25, 26, 28-30, 35, 36).…”

mentioning

confidence: 99%

Effects of Aging on Influenza Virus Infection Dynamics

Hernandez‐Vargas

Wilk

Canini

et al. 2014

J Virol

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125

119

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The consequences of influenza virus infection are generally more severe in individuals over 65 years of age (the elderly). Immunosenescence enhances the susceptibility to viral infections and renders vaccination less effective. Understanding age-related changes in the immune system is crucial in order to design prophylactic and immunomodulatory strategies to reduce morbidity and mortality in the elderly. Here, we propose different mathematical models to provide a quantitative understanding of the immune strategies in the course of influenza virus infection using experimental data from young and aged mice. Simulation results suggested a central role of CD8 ؉ T cells for adequate viral clearance kinetics in young and aged mice. Adding the removal of infected cells by natural killer cells did not improve the model fit in either young or aged animals. We separately examined the infection-resistant state of cells promoted by the cytokines alpha/beta interferon (IFN-␣/␤), IFN-␥, and tumor necrosis factor alpha (TNF-␣). The combination of activated CD8؉ T cells with any of the cytokines provided the best fits in young and aged animals. During the first 3 days after infection, the basic reproductive number for aged mice was 1.5-fold lower than that for young mice (P < 0.05). IMPORTANCEThe fits of our models to the experimental data suggest that the increased levels of IFN-␣/␤, IFN-␥, and TNF-␣ (the "inflammaging" state) promote slower viral growth in aged mice, which consequently limits the stimulation of immune cells and contributes to the reported impaired responses in the elderly. A quantitative understanding of influenza virus pathogenesis and its shift in the elderly is the key contribution of this work.

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Influenza A virus infection kinetics: quantitative data and models

Cited by 153 publications

References 104 publications

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Competitive Fitness of Influenza B Viruses with Neuraminidase Inhibitor-Resistant Substitutions in a Coinfection Model of the Human Airway Epithelium

Effects of Aging on Influenza Virus Infection Dynamics

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