Host genes and influenza pathogenesis in humans: an emerging paradigm

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Highlights

•

Host genes play an important role in the pathogenesis of influenza virus infection.
•

High-throughput technologies accelerate the discovery of susceptibility genes.
•

Host susceptibility studies facilitate the development of host-targeted therapy.
•

Host-targeted therapy may allow individualized treatment for influenza.

Abstract

The emergence of the pandemic influenza virus A(H1N1)pdm09 in 2009 and avian influenza virus A(H7N9) in 2013 provided unique opportunities for assessing genetic predispositions to severe disease because many patients did not have any underlying risk factor or neutralizing antibody against these agents, in contrast to seasonal influenza viruses. High-throughput screening platforms and large human or animal databases from international collaborations allow rapid selection of potential candidate genes for confirmatory functional studies. In the last 2 years, at least seven new human susceptibility genes have been identified in genetic association studies. Integration of knowledge from genetic and phenotypic studies is essential to identify important gene targets for treatment and prevention of influenza virus infection.

Related collections

Most cited references 73

Record: found
Abstract: found
Article: not found

Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease.

Jasper F W Chan, Susanna Lau, Kelvin K. W. To … (2015)

The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.

0 comments Cited 487 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Methods of integrating data to uncover genotype-phenotype interactions.

Marylyn D Ritchie, Emily R. Holzinger, Ruowang Li … (2015)

Recent technological advances have expanded the breadth of available omic data, from whole-genome sequencing data, to extensive transcriptomic, methylomic and metabolomic data. A key goal of analyses of these data is the identification of effective models that predict phenotypic traits and outcomes, elucidating important biomarkers and generating important insights into the genetic underpinnings of the heritability of complex traits. There is still a need for powerful and advanced analysis strategies to fully harness the utility of these comprehensive high-throughput data, identifying true associations and reducing the number of false associations. In this Review, we explore the emerging approaches for data integration - including meta-dimensional and multi-staged analyses - which aim to deepen our understanding of the role of genetics and genomics in complex outcomes. With the use and further development of these approaches, an improved understanding of the relationship between genomic variation and human phenotypes may be revealed.

0 comments Cited 343 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection

John R. Teijaro, Kevin B. Walsh, Stuart Cahalan … (2011)

Summary Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P1 receptor, we elucidate cellular and signaling mechanisms that are important in initiating cytokine storm. Whereas S1P1 receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P1 agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte-deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events that are both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable.

0 comments Cited 293 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Kwok-Yung Yuen

Journal

Journal ID (nlm-ta): Curr Opin Virol

Journal ID (iso-abbrev): Curr Opin Virol

Title: Current Opinion in Virology

Publisher: Elsevier

ISSN (Print): 1879-6257

ISSN (Electronic): 1879-6265

Publication date PMC-release: 14 June 2015

Publication date (Print): October 2015

Publication date (Electronic): 14 June 2015

Volume: 14

Pages: 7-15

Affiliations

[0005]State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Research Centre of Infection and Immunology, Department of Microbiology, The University of Hong Kong, Hong Kong, China

Article

Publisher ID: S1879-6257(15)00076-0

DOI: 10.1016/j.coviro.2015.04.010

PMC ID: 7102748

PubMed ID: 26079652

SO-VID: 570f5fe1-12d2-4ebb-a694-89c0163d95b2

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Host genes and influenza pathogenesis in humans: an emerging paradigm

Read this article at

Highlights

Abstract

Related collections

Genes & Diseases

Most cited references 73

Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease.

Methods of integrating data to uncover genotype-phenotype interactions.

Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 164

Cited by 13

Most referenced authors 1,586