CD8 + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in Vivo, and many revert after transmission

Philip A. Mudd, Adam J. Ericsen, Andrew D. Walsh, Enrique J. León, Nancy A. Wilson, Nicholas J. Maness, Thomas C. Friedrich, David Watkins

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Virus-specific CD8 + T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.

Original languageEnglish
Pages (from-to)12804-12810
Number of pages7
JournalJournal of Virology
Volume85
Issue number23
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
T-lymphocytes
T-Lymphocytes
mutation
Mutation
Human immunodeficiency virus
major histocompatibility complex
Viruses
Major Histocompatibility Complex
viruses
epitopes
HIV
T-Lymphocyte Epitopes
Epitopes
Vaccines
Alleles
vaccines
alleles

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

CD8 + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in Vivo, and many revert after transmission. / Mudd, Philip A.; Ericsen, Adam J.; Walsh, Andrew D.; León, Enrique J.; Wilson, Nancy A.; Maness, Nicholas J.; Friedrich, Thomas C.; Watkins, David.

In: Journal of Virology, Vol. 85, No. 23, 01.12.2011, p. 12804-12810.

Research output: Contribution to journalArticle

Mudd, Philip A. ; Ericsen, Adam J. ; Walsh, Andrew D. ; León, Enrique J. ; Wilson, Nancy A. ; Maness, Nicholas J. ; Friedrich, Thomas C. ; Watkins, David. / CD8 + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in Vivo, and many revert after transmission. In: Journal of Virology. 2011 ; Vol. 85, No. 23. pp. 12804-12810.
@article{cb5df7df213548d4809994befa52a44b,
title = "CD8 + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in Vivo, and many revert after transmission",
abstract = "Virus-specific CD8 + T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27{\%} of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.",
author = "Mudd, {Philip A.} and Ericsen, {Adam J.} and Walsh, {Andrew D.} and Le{\'o}n, {Enrique J.} and Wilson, {Nancy A.} and Maness, {Nicholas J.} and Friedrich, {Thomas C.} and David Watkins",
year = "2011",
month = "12",
day = "1",
doi = "10.1128/JVI.05841-11",
language = "English",
volume = "85",
pages = "12804--12810",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - CD8 + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in Vivo, and many revert after transmission

AU - Mudd, Philip A.

AU - Ericsen, Adam J.

AU - Walsh, Andrew D.

AU - León, Enrique J.

AU - Wilson, Nancy A.

AU - Maness, Nicholas J.

AU - Friedrich, Thomas C.

AU - Watkins, David

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Virus-specific CD8 + T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.

AB - Virus-specific CD8 + T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.

UR - http://www.scopus.com/inward/record.url?scp=81255163673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81255163673&partnerID=8YFLogxK

U2 - 10.1128/JVI.05841-11

DO - 10.1128/JVI.05841-11

M3 - Article

C2 - 21957309

AN - SCOPUS:81255163673

VL - 85

SP - 12804

EP - 12810

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -