HIV subtype influences HLA-B*07:02-associated HIV disease outcome

Henrik N Kløverpris; Emily Adland; Madoka Koyanagi; Anette Stryhn Buus; Mikkel Harndahl; Philippa C Matthews; Roger Shapiro; Bruce D Walker; Thumbi Ndung'u; Christian Brander; Masafumi Takiguchi; Søren Buus; Philip Goulder

doi:10.1089/AID.2013.0197

HIV subtype influences HLA-B*07:02-associated HIV disease outcome

Henrik N Kløverpris, Emily Adland, Madoka Koyanagi, Anette Stryhn Buus, Mikkel Harndahl, Philippa C Matthews, Roger Shapiro, Bruce D Walker, Thumbi Ndung'u, Christian Brander, Masafumi Takiguchi, Søren Buus, Philip Goulder

16 Citations (Scopus)

Abstract

Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag "GL9" (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.

Original language	English
Journal	AIDS Research and Human Retroviruses
Volume	30
Issue number	5
Pages (from-to)	468-75
Number of pages	8
ISSN	0889-2229
DOIs	https://doi.org/10.1089/AID.2013.0197
Publication status	Published - 30 May 2014

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title = "HIV subtype influences HLA-B*07:02-associated HIV disease outcome",

abstract = "Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag {"}GL9{"} (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.",

author = "Kl{\o}verpris, {Henrik N} and Emily Adland and Madoka Koyanagi and Buus, {Anette Stryhn} and Mikkel Harndahl and Matthews, {Philippa C} and Roger Shapiro and Walker, {Bruce D} and Thumbi Ndung'u and Christian Brander and Masafumi Takiguchi and S{\o}ren Buus and Philip Goulder",

year = "2014",

month = may,

day = "30",

doi = "10.1089/AID.2013.0197",

language = "English",

volume = "30",

pages = "468--75",

journal = "AIDS Research and Human Retroviruses",

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TY - JOUR

T1 - HIV subtype influences HLA-B*07:02-associated HIV disease outcome

AU - Kløverpris, Henrik N

AU - Adland, Emily

AU - Koyanagi, Madoka

AU - Buus, Anette Stryhn

AU - Harndahl, Mikkel

AU - Matthews, Philippa C

AU - Shapiro, Roger

AU - Walker, Bruce D

AU - Ndung'u, Thumbi

AU - Brander, Christian

AU - Takiguchi, Masafumi

AU - Buus, Søren

AU - Goulder, Philip

PY - 2014/5/30

Y1 - 2014/5/30

N2 - Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag "GL9" (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.

AB - Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag "GL9" (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.

U2 - 10.1089/AID.2013.0197

DO - 10.1089/AID.2013.0197

M3 - Journal article

C2 - 24010680

SN - 0889-2229

VL - 30

SP - 468

EP - 475

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

IS - 5

ER -

HIV subtype influences HLA-B*07:02-associated HIV disease outcome

Abstract

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