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| Status |
Public on Sep 10, 2018 |
| Title |
Host chaperones can define the fitness of adaptive influenza variants |
| Organism |
Canis lupus familiaris |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The threat of viral pandemics demands a comprehensive understanding of evolution at the host-pathogen interface. Here, we systematically show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which is conserved across human flu strains, confers resistance to the MxA antiviral-restriction factor, and critically contributed to the pathogenicity of the 1918 pandemic flu, is rendered unfit by host chaperone depletion. This fitness loss is linked to biophysical defects that chaperones cannot address when heat shock factor-I is inhibited. Thus, host chaperones can be hijacked by viruses to un-couple biophysically deleterious consequences of mutations from the benefits of immune escape. In summary, host chaperones play a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host-switching, and for the design of antiviral strategies refractory to resistance.
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| Overall design |
Three replicates each of MDCK cells transduced with inducible inhibitor of HSF1 in the presence or absence of Doxycycline at 37 or 39 degrees C.
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| Contributor(s) |
Ponomarenko AI, Phillips AM, Chen K, Ashenberg OL, Miao J, McHugh SM, Butty VL, Whittaker CA, Moore CL, Bloom JD, Lin Y, Shoulders MD |
| Citation missing |
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| Submission date |
Apr 25, 2018 |
| Last update date |
Sep 10, 2018 |
| Contact name |
Charles Arthur Whittaker |
| E-mail(s) |
charliew@mit.edu
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| Organization name |
Koch Institute
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| Street address |
77 Mass Ave 76-189
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02152 |
| Country |
USA |
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| Platforms (1) |
| GPL16540 |
Illumina HiSeq 2000 (Canis lupus familiaris) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA453534 |
| SRA |
SRP142600 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113649_annapon_counts.txt.gz |
362.6 Kb |
(ftp)(http) |
TXT |
| GSE113649_annapon_l2tpm.txt.gz |
668.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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