Dataset Information

Coronaviruses and the human airway: a universal system for virus-host interaction studies.

ABSTRACT: Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.

SUBMITTER: Jonsdottir HR

PROVIDER: S-EPMC4744394 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Coronaviruses and the human airway: a universal system for virus-host interaction studies.

Jonsdottir Hulda R HR Dijkman Ronald R

Virology journal 20160206

Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infectio ...[more]

PMID: 26852031

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Project description:Positive single-strand ribonucleic acid [(+)ssRNA] viruses can cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are tightly connected, generating a complex dynamics that conveys in virion assembly to ensure virus spread in the body. Starting from the knowledge of relevant processes in (+ss)RNA virus replication, transcription, translation, virions budding and shedding, and their respective energy costs, we built up a systems thinking (ST)-based diagram of the virus-host interaction, comprehensive of stocks, flows, and processes as well-described in literature. In ST approach, stocks and flows are expressed by a proxy of the energy embedded and transmitted, respectively, whereas processes are referred to the energy required for the system functioning. In this perspective, healthiness is just a particular configuration, in which stocks relevant for the system (equivalent but not limited to proteins, RNA, DNA, and all metabolites required for the survival) are constant, and the system behavior is stationary. At time of infection, the presence of additional stocks (e.g., viral protein and RNA and all metabolites required for virion assembly and spread) confers a complex network of feedbacks leading to new configurations, which can evolve to maximize the virions stock, thus changing the system structure, output, and purpose. The dynamic trajectories will evolve to achieve a new stationary status, a phenomenon described in microbiology as integration and symbiosis when the system is resilient enough to the changes, or the system may stop functioning and die. Application of external driving forces, acting on processes, can affect the dynamic trajectories adding a further degree of complexity, which can be captured by ST approach, used to address these new configurations. Investigation of system configurations in response to external driving forces acting is developed by computational analysis based on ST diagrams, with the aim at designing novel therapeutic approaches.

Dataset Information

Coronaviruses and the human airway: a universal system for virus-host interaction studies.

Publications

Coronaviruses and the human airway: a universal system for virus-host interaction studies.

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