Abstract
Nef-mediated down-regulation of MHC class I (MHC-I) molecules on HIV-1-infected cells has been proposed to enhance viral persistence through evasion of host CTLs. This conclusion is based largely on demonstrations that Nef from laboratory HIV-1 strains reduces the susceptibility of infected cells to CTL killing in vitro. However, the function and role of Nef-mediated MHC-I down-regulation in vivo have not been well described. To approach this issue, nef quasispecies from chronically HIV-1-infected individuals were cloned into recombinant reporter viruses and tested for their ability to down-regulate MHC-I molecules from the surface of infected cells. The level of function varied widely between individuals, and although comparison to the immunologic parameters of blood CD4(+) T lymphocyte count and breadth of the HIV-1-specific CTL response showed positive correlations, no significant correlation was found in comparison to plasma viremia. The ability of in vivo-derived Nef to down-regulate MHC-I predicted the resistance of HIV-1 to suppression by CTL. Taken together, these data demonstrate the functionality of Nef to down-regulate MHC-I in vivo during stable chronic infection, and suggest that this function is maintained by the need of HIV-1 to cope with the antiviral CTL response.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Adaptation, Physiological / immunology*
-
Adult
-
Cytotoxicity, Immunologic
-
Disease Progression
-
Down-Regulation / immunology
-
Epitopes, T-Lymphocyte / immunology
-
HIV Infections / immunology*
-
HIV Infections / virology
-
HIV-1 / immunology*
-
HIV-1 / metabolism
-
HLA-A Antigens / biosynthesis
-
HLA-A Antigens / metabolism
-
HLA-A2 Antigen
-
Humans
-
Male
-
Middle Aged
-
Molecular Sequence Data
-
Phylogeny
-
Predictive Value of Tests
-
T-Lymphocytes, Cytotoxic / immunology
-
T-Lymphocytes, Cytotoxic / virology
-
Viral Load
-
nef Gene Products, Human Immunodeficiency Virus / blood
-
nef Gene Products, Human Immunodeficiency Virus / physiology*
Substances
-
Epitopes, T-Lymphocyte
-
HLA-A Antigens
-
HLA-A*02 antigen
-
HLA-A2 Antigen
-
nef Gene Products, Human Immunodeficiency Virus
-
nef protein, Human immunodeficiency virus 1
Associated data
-
GENBANK/EU327403
-
GENBANK/EU327404
-
GENBANK/EU327405
-
GENBANK/EU327406
-
GENBANK/EU327407
-
GENBANK/EU327408
-
GENBANK/EU327409
-
GENBANK/EU327410
-
GENBANK/EU327411
-
GENBANK/EU327412
-
GENBANK/EU327413
-
GENBANK/EU327414
-
GENBANK/EU327415
-
GENBANK/EU327416
-
GENBANK/EU327417
-
GENBANK/EU327418
-
GENBANK/EU327419
-
GENBANK/EU327420
-
GENBANK/EU327421
-
GENBANK/EU327422
-
GENBANK/EU327423
-
GENBANK/EU327424
-
GENBANK/EU327425
-
GENBANK/EU327426
-
GENBANK/EU327427
-
GENBANK/EU327428
-
GENBANK/EU327429
-
GENBANK/EU327430
-
GENBANK/EU327431
-
GENBANK/EU327432
-
GENBANK/EU327433
-
GENBANK/EU327434
-
GENBANK/EU327435
-
GENBANK/EU327436
-
GENBANK/EU327437
-
GENBANK/EU327438
-
GENBANK/EU327439
-
GENBANK/EU327440
-
GENBANK/EU327441
-
GENBANK/EU327442
-
GENBANK/EU327443
-
GENBANK/EU327444
-
GENBANK/EU327445
-
GENBANK/EU327446
-
GENBANK/EU327447
-
GENBANK/EU327448
-
GENBANK/EU327449
-
GENBANK/EU327450
-
GENBANK/EU327451
-
GENBANK/EU327452
-
GENBANK/EU327453
-
GENBANK/EU327454
-
GENBANK/EU327455
-
GENBANK/EU327456
-
GENBANK/EU327457
-
GENBANK/EU327458
-
GENBANK/EU327459
-
GENBANK/EU327460
-
GENBANK/EU327461
-
GENBANK/EU327462
-
GENBANK/EU327463
-
GENBANK/EU327464
-
GENBANK/EU327465
-
GENBANK/EU327466
-
GENBANK/EU327467
-
GENBANK/EU327468
-
GENBANK/EU327469
-
GENBANK/EU327470
-
GENBANK/EU327471
-
GENBANK/EU327472
-
GENBANK/EU327473
-
GENBANK/EU327474
-
GENBANK/EU327475
-
GENBANK/EU327476
-
GENBANK/EU327477
-
GENBANK/EU327478
-
GENBANK/EU327479
-
GENBANK/EU327480
-
GENBANK/EU327481
-
GENBANK/EU327482
-
GENBANK/EU327483
-
GENBANK/EU327484
-
GENBANK/EU327485
-
GENBANK/EU327486
-
GENBANK/EU327487
-
GENBANK/EU327488
-
GENBANK/EU327489
-
GENBANK/EU327490
-
GENBANK/EU327491
-
GENBANK/EU327492