Escape from CD8 + T cell responses in Mamu-B*00801 + macaques differentiates progressors from elite controllers

Philip A. Mudd, Adam J. Ericsen, Benjamin J. Burwitz, Nancy A. Wilson, David H. O'Connor, Austin L. Hughes, David Watkins

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

A small number of HIV-infected individuals known as elite controllers experience low levels of chronic phase viral replication and delayed progression to AIDS. Specific HLA class I alleles are associated with elite control, implicating CD8 + T lymphocytes in the establishment of these low levels of viral replication. Most HIV-infected individuals that express protective HLA class I alleles, however, do not control viral replication. Approximately 50% of Mamu-B*00801 + Indian rhesus macaques control SIVmac239 replication in the chronic phase in a manner that resembles elite control in humans. We followed both the immune response and viral evolution in SIV-infected Mamu-B*00801 + animals to better understand the role of CD8 + T lymphocytes during the acute phase of viral infection, when viral control status is determined. The virus escaped from immunodominant Vif and Nef Mamu- B*00801-restricted CD8 + T lymphocyte responses during the critical early weeks of acute infection only in progressor animals that did not control viral replication. Thus, early CD8 + T lymphocyte escape is a hallmark of Mamu-B*00801 + macaques who do not control viral replication. By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8 + T lymphocytes, implying that these cells play a role in viral control.

Original languageEnglish
Pages (from-to)3364-3370
Number of pages7
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012

Fingerprint

Macaca
T-Lymphocytes
Alleles
HIV
Viruses
Immunodominant Epitopes
Virus Diseases
Macaca mulatta
Acquired Immunodeficiency Syndrome
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Escape from CD8 + T cell responses in Mamu-B*00801 + macaques differentiates progressors from elite controllers. / Mudd, Philip A.; Ericsen, Adam J.; Burwitz, Benjamin J.; Wilson, Nancy A.; O'Connor, David H.; Hughes, Austin L.; Watkins, David.

In: Journal of Immunology, Vol. 188, No. 7, 01.04.2012, p. 3364-3370.

Research output: Contribution to journalArticle

Mudd, Philip A. ; Ericsen, Adam J. ; Burwitz, Benjamin J. ; Wilson, Nancy A. ; O'Connor, David H. ; Hughes, Austin L. ; Watkins, David. / Escape from CD8 + T cell responses in Mamu-B*00801 + macaques differentiates progressors from elite controllers. In: Journal of Immunology. 2012 ; Vol. 188, No. 7. pp. 3364-3370.
@article{0d5d1e4363284575888646c73a535a89,
title = "Escape from CD8 + T cell responses in Mamu-B*00801 + macaques differentiates progressors from elite controllers",
abstract = "A small number of HIV-infected individuals known as elite controllers experience low levels of chronic phase viral replication and delayed progression to AIDS. Specific HLA class I alleles are associated with elite control, implicating CD8 + T lymphocytes in the establishment of these low levels of viral replication. Most HIV-infected individuals that express protective HLA class I alleles, however, do not control viral replication. Approximately 50{\%} of Mamu-B*00801 + Indian rhesus macaques control SIVmac239 replication in the chronic phase in a manner that resembles elite control in humans. We followed both the immune response and viral evolution in SIV-infected Mamu-B*00801 + animals to better understand the role of CD8 + T lymphocytes during the acute phase of viral infection, when viral control status is determined. The virus escaped from immunodominant Vif and Nef Mamu- B*00801-restricted CD8 + T lymphocyte responses during the critical early weeks of acute infection only in progressor animals that did not control viral replication. Thus, early CD8 + T lymphocyte escape is a hallmark of Mamu-B*00801 + macaques who do not control viral replication. By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8 + T lymphocytes, implying that these cells play a role in viral control.",
author = "Mudd, {Philip A.} and Ericsen, {Adam J.} and Burwitz, {Benjamin J.} and Wilson, {Nancy A.} and O'Connor, {David H.} and Hughes, {Austin L.} and David Watkins",
year = "2012",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1102470",
language = "English",
volume = "188",
pages = "3364--3370",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Escape from CD8 + T cell responses in Mamu-B*00801 + macaques differentiates progressors from elite controllers

AU - Mudd, Philip A.

AU - Ericsen, Adam J.

AU - Burwitz, Benjamin J.

AU - Wilson, Nancy A.

AU - O'Connor, David H.

AU - Hughes, Austin L.

AU - Watkins, David

PY - 2012/4/1

Y1 - 2012/4/1

N2 - A small number of HIV-infected individuals known as elite controllers experience low levels of chronic phase viral replication and delayed progression to AIDS. Specific HLA class I alleles are associated with elite control, implicating CD8 + T lymphocytes in the establishment of these low levels of viral replication. Most HIV-infected individuals that express protective HLA class I alleles, however, do not control viral replication. Approximately 50% of Mamu-B*00801 + Indian rhesus macaques control SIVmac239 replication in the chronic phase in a manner that resembles elite control in humans. We followed both the immune response and viral evolution in SIV-infected Mamu-B*00801 + animals to better understand the role of CD8 + T lymphocytes during the acute phase of viral infection, when viral control status is determined. The virus escaped from immunodominant Vif and Nef Mamu- B*00801-restricted CD8 + T lymphocyte responses during the critical early weeks of acute infection only in progressor animals that did not control viral replication. Thus, early CD8 + T lymphocyte escape is a hallmark of Mamu-B*00801 + macaques who do not control viral replication. By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8 + T lymphocytes, implying that these cells play a role in viral control.

AB - A small number of HIV-infected individuals known as elite controllers experience low levels of chronic phase viral replication and delayed progression to AIDS. Specific HLA class I alleles are associated with elite control, implicating CD8 + T lymphocytes in the establishment of these low levels of viral replication. Most HIV-infected individuals that express protective HLA class I alleles, however, do not control viral replication. Approximately 50% of Mamu-B*00801 + Indian rhesus macaques control SIVmac239 replication in the chronic phase in a manner that resembles elite control in humans. We followed both the immune response and viral evolution in SIV-infected Mamu-B*00801 + animals to better understand the role of CD8 + T lymphocytes during the acute phase of viral infection, when viral control status is determined. The virus escaped from immunodominant Vif and Nef Mamu- B*00801-restricted CD8 + T lymphocyte responses during the critical early weeks of acute infection only in progressor animals that did not control viral replication. Thus, early CD8 + T lymphocyte escape is a hallmark of Mamu-B*00801 + macaques who do not control viral replication. By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8 + T lymphocytes, implying that these cells play a role in viral control.

UR - http://www.scopus.com/inward/record.url?scp=84859406226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859406226&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1102470

DO - 10.4049/jimmunol.1102470

M3 - Article

VL - 188

SP - 3364

EP - 3370

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -