Dataset Information

Host genes and influenza pathogenesis in humans: an emerging paradigm.

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.

SUBMITTER: To KK

PROVIDER: S-EPMC7102748 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Host genes and influenza pathogenesis in humans: an emerging paradigm.

To Kelvin Kai-Wang KK Zhou Jie J Chan Jasper Fuk-Woo JF Yuen Kwok-Yung KY

Current opinion in virology 20150614

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 ge ...[more]

PMID: 26079652

Similar Datasets

Project description:Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.

Dataset Information

Host genes and influenza pathogenesis in humans: an emerging paradigm.

Publications

Host genes and influenza pathogenesis in humans: an emerging paradigm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets