Pathogenic conversion of live attenuated simian immunodeficiency virus vaccines is associated with expression of truncated Nef.
Rhesus macaques infected with simian immunodeficiency virus (SIV) containing either a large nef deletion (SIVmac239Delta(152)nef) or interleukin-2 in place of nef developed high virus loads and progressed to simian AIDS. Viruses recovered from both juvenile and neonatal macaques with disease produced a novel truncated Nef protein, tNef. Viruses recovered from juvenile macaques infected with serially passaged virus expressing tNef exhibited a pathogenic phenotype. These findings demonstrated strong selective pressure to restore expression of a truncated Nef protein, and this reversion was linked to increased pathogenic potential in live attenuated SIV vaccines.
Sawai
E T
ET
Department of Medical Pathology, University of California, Davis, California 95616, USA.
Hamza
M S
MS
Ye
M
M
Shaw
K E
KE
Luciw
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D015693:Gene Products, nef / Q000235:genetics*; D005822:Genetic Vectors; D007376:Interleukin-2 / Q000235:genetics; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018449:SAIDS Vaccines / Q000009:adverse effects / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity*; D014613:Vaccines, Attenuated / Q000235:genetics
D015693:Gene Products, nef; D007376:Interleukin-2; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated