Species-specific effects of HIV-1 Nef-mediated MHC-I downmodulation.
In vitro studies have revealed that human immunodeficiency virus-1 (HIV-1) Nef functionally interacts with amino acid residues in the cytoplasmic tail of major histocompatibility complex class I (MHC-I) molecules, reducing their expression on the cell surface and protecting them from cytotoxic T lymphocyte (CTL) lysis. To obtain a better understanding of Nef's effects in vivo, it would be helpful to have a mouse model system. However, it is not known whether Nef will affect murine MHC-I proteins. We find that Nef downmodulates human MHC-I HLA-A2 more efficiently than murine MHC-I molecules in HeLa cells and that Nef does not function efficiently in murine endothelial cells. Studies with chimeric molecules indicate that the MHC-I cytoplasmic tail is primarily responsible for species-specific differences. However, there are also effects attributable to the extracellular domain.
Fleis
Rebekah
R
Department of Medicine, The University of Michigan, Ann Arbor, Michigan 48109, USA.
Filzen
Tracey
T
Collins
Kathleen L
KL
D000595:Amino Acid Sequence; D000818:Animals; D015536:Down-Regulation; D005434:Flow Cytometry; D015693:Gene Products, nef / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D015789:HLA-A2 Antigen / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013045:Species Specificity; D014161:Transduction, Genetic; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus