Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus

Tomek Swigut, Louis Alexander, Jennifer Morgan, Jeff Lifson, Keith G. Mansfield, Sabine Lang, R. Paul Johnson, Jacek Skowronski, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

Original languageEnglish (US)
Pages (from-to)13335-13344
Number of pages10
JournalJournal of Virology
Volume78
Issue number23
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
major histocompatibility complex
Major Histocompatibility Complex
Down-Regulation
immune response
monkeys
Haplorhini
mutation
viruses
Human immunodeficiency virus
lymphocyte proliferation
nef Gene Products
membrane proteins
Viruses
blood proteins
Mutation
plasma membrane
T-lymphocytes
Lymphocyte Activation

ASJC Scopus subject areas

  • Immunology

Cite this

Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus. / Swigut, Tomek; Alexander, Louis; Morgan, Jennifer; Lifson, Jeff; Mansfield, Keith G.; Lang, Sabine; Johnson, R. Paul; Skowronski, Jacek; Desrosiers, Ronald Charles.

In: Journal of Virology, Vol. 78, No. 23, 12.2004, p. 13335-13344.

Research output: Contribution to journalArticle

Swigut, Tomek ; Alexander, Louis ; Morgan, Jennifer ; Lifson, Jeff ; Mansfield, Keith G. ; Lang, Sabine ; Johnson, R. Paul ; Skowronski, Jacek ; Desrosiers, Ronald Charles. / Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus. In: Journal of Virology. 2004 ; Vol. 78, No. 23. pp. 13335-13344.
@article{deafed39de494921a6ec5798f45ff002,
title = "Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus",
abstract = "Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.",
author = "Tomek Swigut and Louis Alexander and Jennifer Morgan and Jeff Lifson and Mansfield, {Keith G.} and Sabine Lang and Johnson, {R. Paul} and Jacek Skowronski and Desrosiers, {Ronald Charles}",
year = "2004",
month = "12",
doi = "10.1128/JVI.78.23.13335-13344.2004",
language = "English (US)",
volume = "78",
pages = "13335--13344",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus

AU - Swigut, Tomek

AU - Alexander, Louis

AU - Morgan, Jennifer

AU - Lifson, Jeff

AU - Mansfield, Keith G.

AU - Lang, Sabine

AU - Johnson, R. Paul

AU - Skowronski, Jacek

AU - Desrosiers, Ronald Charles

PY - 2004/12

Y1 - 2004/12

N2 - Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

AB - Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

UR - http://www.scopus.com/inward/record.url?scp=8644289282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8644289282&partnerID=8YFLogxK

U2 - 10.1128/JVI.78.23.13335-13344.2004

DO - 10.1128/JVI.78.23.13335-13344.2004

M3 - Article

C2 - 15542684

AN - SCOPUS:8644289282

VL - 78

SP - 13335

EP - 13344

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -