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 language | English (US) |
|---|---|
| Pages (from-to) | 13335-13344 |
| Number of pages | 10 |
| Journal | Journal of Virology |
| Volume | 78 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 2004 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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 -