Efficient class I major histocompatibility complex down-regulation by simian immunodeficiency virus Nef is associated with a strong selective advantage in infected rhesus macaques.
Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.
Münch
J
J
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Stolte
N
N
Fuchs
D
D
Stahl-Hennig
C
C
Kirchhoff
F
F
D000818:Animals; D015536:Down-Regulation; D015693:Gene Products, nef / Q000737:chemistry / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013329:Structure-Activity Relationship; D014779:Virus Replication
D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I