Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response

Fribourg, Miguel; Hartmann, Boris; Schmolke, Mirco; Marjanović, Nada; Albrecht, Randy A.; Garcı́a-Sastre, Adolfo; Sealfon, Stuart C.; Jayaprakash, C.; Hayot, F.

doi:10.1016/j.jtbi.2014.02.029

Cited by 17 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another extension involves going from vaccination to natural infection. This will involve incorporating resource (target cells) limitation and innate immunity [ 34 – 38 ] as well as T cells [ 39 – 41 ]. These models could be used to consider the effect of pre-existing antibodies on infection with drifted and shifted virus strains.…”

Section: Discussionmentioning

confidence: 99%

Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

et al. 2016

View full text Add to dashboard Cite

The development of next-generation influenza vaccines that elicit strain-transcendent immunity against both seasonal and pandemic viruses is a key public health goal. Targeting the evolutionarily conserved epitopes on the stem of influenza’s major surface molecule, hemagglutinin, is an appealing prospect, and novel vaccine formulations show promising results in animal model systems. However, studies in humans indicate that natural infection and vaccination result in limited boosting of antibodies to the stem of HA, and the level of stem-specific antibody elicited is insufficient to provide broad strain-transcendent immunity. Here, we use mathematical models of the humoral immune response to explore how pre-existing immunity affects the ability of vaccines to boost antibodies to the head and stem of HA in humans, and, in particular, how it leads to the apparent lack of boosting of broadly cross-reactive antibodies to the stem epitopes. We consider hypotheses where binding of antibody to an epitope: (i) results in more rapid clearance of the antigen; (ii) leads to the formation of antigen-antibody complexes which inhibit B cell activation through Fcγ receptor-mediated mechanism; and (iii) masks the epitope and prevents the stimulation and proliferation of specific B cells. We find that only epitope masking but not the former two mechanisms to be key in recapitulating patterns in data. We discuss the ramifications of our findings for the development of vaccines against both seasonal and pandemic influenza.

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We believe that these findings contribute to an improved understanding of IFN induction and control by IAVs. They will be valuable not only to explain strain-dependent differences in biological responses to IAV infection downstream of IFN signaling, such as inflammasome and TRAIL induction (59,60), but also for interpretations of NS1 mutant phenotypes (61) and the refinement of mathematical models concerning viral IFN induction (37,62).…”

Section: Discussionmentioning

confidence: 99%

Fluorescence-Activated Cell Sorting-Based Analysis Reveals an Asymmetric Induction of Interferon-Stimulated Genes in Response to Seasonal Influenza A Virus

Recum-Knepper

Sadewasser

Weinheimer

et al. 2015

J Virol

View full text Add to dashboard Cite

Influenza A virus (IAV) infection provokes an antiviral response involving the expression of type I and III interferons (IFN) and Influenza A viruses (IAVs) are prototypic members of the Orthomyxoviridae family, featuring a segmented RNA genome composed of eight single-stranded RNAs that have negative polarity (1). IAVs circulate in the human population, causing periodic epidemic outbreaks and occasional pandemic waves of respiratory disease (2). Moreover, there is a large natural IAV host reservoir in wild aquatic birds, such as ducks and geese, in which the viruses cause mainly mild or no apparent symptoms. IAV strains are usually well adapted to their particular host species, which is reflected not only in the existence of stable virus lineages but also in polymorphic amino acid positions in viral proteins distinctively found in human or avian strains (3).IAVs target the epithelial cell layers lining the human respiratory tract, in which they are subject to immune control in infected cells, mediated by the antiviral type I interferon (IFN) response (4). Many of the key events and factors driving the IFN response have been identified and involve initial recognition of the viral genomic 5=-triphosphorylated RNA by the intracellular RNA helicase RIG-I, which governs a signaling module culminating in the activation of transcription factors, such as IRF-3 and NF-B, thereby inducing the transcription of type I IFN genes (5, 6). Type I IFNs comprise 14 subtypes of IFN-␣ and one IFN-␤ that are secreted from virus-infected cells and exert antiviral effects against many virus families, including IAV (4, 7). Type I IFNs secreted by

show abstract

“…Such signaling can trigger both autocrine and paracrine cellular responses that shut down protein synthesis that is essential for expression of essential viral functions. Different facets of such responses have been quantified and modeled mechanistically, including initial sensing of the viral dsRNA (139), induction of IFNs that activate both positive and negative feedbacks (140), and responses to different degrees of viral antagonism (141). Notably, in the case of infections by the highly pathogenic Nipah virus, modeling of the host response along with transcription-level measures of IFN and inflammatory cytokine activation provided insight by suggesting that the virus may delay suppression of inflammation and thereby enhance vascular permeability and infection spread (142).…”

Section: Host Cell Physiology and Innate Immune Responsesmentioning

confidence: 99%

Kinetic Modeling of Virus Growth in Cells

Yin

Redovich

2018

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

When a virus infects a host cell, it hijacks the biosynthetic capacity of the cell to produce virus progeny, a process that may take less than an hour or more than a week. The overall time required for a virus to reproduce depends collectively on the rates of multiple steps in the infection process, including initial binding of the virus particle to the surface of the cell, virus internalization and release of the viral genome within the cell, decoding of the genome to make viral proteins, replication of the genome, assembly of progeny virus particles, and release of these particles into the extracellular environment. For a large number of virus types, much has been learned about the molecular mechanisms and rates of the various steps. However, in only relatively few cases during the last 50 years has an attempt been made-using mathematical modeling-to account for how the different steps contribute to the overall timing and productivity of the infection cycle in a cell. Here we review the initial case studies, which include studies of the one-step growth behavior of viruses that infect bacteria (Qβ, T7, and M13), human immunodeficiency virus, influenza A virus, poliovirus, vesicular stomatitis virus, baculovirus, hepatitis B and C viruses, and herpes simplex virus. Further, we consider how such models enable one to explore how cellular resources are utilized and how antiviral strategies might be designed to resist escape. Finally, we highlight challenges and opportunities at the frontiers of cell-level modeling of virus infections.

show abstract

Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response

Cited by 17 publications

References 28 publications

Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

Fluorescence-Activated Cell Sorting-Based Analysis Reveals an Asymmetric Induction of Interferon-Stimulated Genes in Response to Seasonal Influenza A Virus

Kinetic Modeling of Virus Growth in Cells

Contact Info

Product

Resources

About