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Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control.

Journal Article
1061-4036
666-673
Ansari, M. Azim
6bc3f987-64de-4be7-81c4-bedf1ecb7059
Pedergnana, Vincent
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Ip, Camilla L.C.
dcf4ebb3-0b2c-44d1-84ef-b479c4cc4cd6
Magri, Andrea
afa1be77-b814-4b34-822c-bd391942cf26
Von Delft, Annette
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Bonsall, David
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Chaturvedi, Nimisha
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Bartha, Istvan
483efb81-4897-4922-a6fe-ed786204f0b3
Smith, David
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Nicholson, George
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McVean, Gilean
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Trebes, Amy
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Piazza, Paolo
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Fellay, Jacques
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Cooke, Graham
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Foster, Graham R.
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Hudson, Emma
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McLauchlan, John
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Simmonds, Peter
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Bowden, Rory
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Klenerman, Paul
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Barnes, Eleanor
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Spencer, Chris C.A.
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[error in script]
Ansari, M. Azim
6bc3f987-64de-4be7-81c4-bedf1ecb7059
Pedergnana, Vincent
84922119-6687-4ab4-a4d2-5dbe6a78652f
Ip, Camilla L.C.
dcf4ebb3-0b2c-44d1-84ef-b479c4cc4cd6
Magri, Andrea
afa1be77-b814-4b34-822c-bd391942cf26
Von Delft, Annette
0bd30491-7e18-46de-9dcb-d0fcded6dfd8
Bonsall, David
d9757249-4624-4e64-bba8-dd2308bc2e41
Chaturvedi, Nimisha
63fc450d-39ee-4575-b6c7-b468605eb05e
Bartha, Istvan
483efb81-4897-4922-a6fe-ed786204f0b3
Smith, David
18f2f976-3109-4519-9d94-1d3475558b54
Nicholson, George
73b465b0-9163-4abb-a56e-ea3f8c3c0295
McVean, Gilean
5c8f1bd8-9772-4ba3-807c-1a7e317fccff
Trebes, Amy
04fd3206-d8de-4b0d-9fa0-6a5e3247f549
Piazza, Paolo
f09e07ff-2f20-458d-8ffa-3b8ce919c6d6
Fellay, Jacques
be4cf13e-1ae6-4e88-85f8-e899f04e2b02
Cooke, Graham
a732b437-ff1f-4da0-a505-f7297adefdf4
Foster, Graham R.
02706339-bf67-4d05-b1d3-a16c54245008
Hudson, Emma
f3298804-a298-4fcf-9c00-ab554501a3a0
McLauchlan, John
bbd0b652-5cfb-40ea-afac-1ed7cd85a238
Simmonds, Peter
27d4c068-e352-4cbf-9899-771893788ade
Bowden, Rory
daedf938-2679-483a-83b4-f99b75fbf807
Klenerman, Paul
aa4c00a6-1a4d-4a4f-ac21-2131996344a7
Barnes, Eleanor
2ccdaa43-22ce-4cb1-91ca-2abb35df1966
Spencer, Chris C.A.
6bab753b-bcb7-41d8-a79b-8e3c904c6aef

Ansari, M. Azim, Pedergnana, Vincent, Ip, Camilla L.C., Magri, Andrea, Von Delft, Annette, Bonsall, David, Chaturvedi, Nimisha, Bartha, Istvan, Smith, David, Nicholson, George, McVean, Gilean, Trebes, Amy, Piazza, Paolo, Fellay, Jacques, Cooke, Graham, Foster, Graham R., Hudson, Emma, McLauchlan, John, Simmonds, Peter, Bowden, Rory, Klenerman, Paul, Barnes, Eleanor and Spencer, Chris C.A. STOP-HCV Consortium (2017) Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus Nature Genetics, 49, (5), pp. 666-673.

Record type: Article

Abstract

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control.

Full text not available from this repository.

More information

Accepted/In Press date: 10 March 2017
e-pub ahead of print date: 10 April 2017
Published date: May 2017
Keywords: Journal Article

Identifiers

Local EPrints ID: 413488
URI: http://eprints.soton.ac.uk/id/eprint/413488
ISSN: 1061-4036
PURE UUID: 9f3a66a2-db88-4489-a7ee-653fae689be9

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Date deposited: 24 Aug 2017 16:31
Last modified: 31 Oct 2017 22:49

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Contributors

Author: M. Azim Ansari
Author: Vincent Pedergnana
Author: Camilla L.C. Ip
Author: Andrea Magri
Author: Annette Von Delft
Author: David Bonsall
Author: Nimisha Chaturvedi
Author: Istvan Bartha
Author: David Smith
Author: George Nicholson
Author: Gilean McVean
Author: Amy Trebes
Author: Paolo Piazza
Author: Jacques Fellay
Author: Graham Cooke
Author: Graham R. Foster
Author: Emma Hudson
Author: John McLauchlan
Author: Peter Simmonds
Author: Rory Bowden
Author: Paul Klenerman
Author: Eleanor Barnes
Author: Chris C.A. Spencer

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