T-cell receptor:CD3 down-regulation is a selected in vivo function of simian immunodeficiency virus Nef but is not sufficient for effective viral replication in rhesus macaques.
We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T. Sawai, M. S. Hamza, M. Ye, K. E. Shaw, and P. A. Luciw, J. Virol. 74:2038-2045, 2000). We found that the tNef proteins were unable to down-regulate the cell surface expression of major histocompatibility complex class I proteins, CD4, and CD28 and neither stimulated SIV replication nor enhanced virion infectivity. The tNef proteins did efficiently down-regulate T-cell receptor (TCR):CD3 cell surface expression. Nevertheless, the SIVmac239 tnef variants were strongly attenuated in six infected juvenile rhesus macaques. Thus, while the ability of SIV Nef to down-modulate TCR:CD3 cell surface expression apparently confers a selective advantage in vivo, it is insufficient for efficient viral replication in infected macaques. Additional mutations elsewhere in SIVmac239 tnef genomes are required for a virulent phenotype.
Münch
Jan
J
Abteilung Virologie, Universitätsklinikum, 89081 Ulm, Germany.
Janardhan
Ajit
A
Stolte
Nicole
N
Stahl-Hennig
Christiane
C
Ten Haaft
Peter
P
Heeney
Jonathan L
JL
Swigut
Tomek
T
Kirchhoff
Frank
F
Skowronski
Jacek
J
D000595:Amino Acid Sequence; D000818:Animals; D015536:Down-Regulation; D015754:Genes, nef; D014644:Genetic Variation; D006801:Humans; D019169:Jurkat Cells; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics / Q000276:immunology / Q000502:physiology*
C429284:NEF protein, SIV; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D054334:Viral Regulatory and Accessory Proteins