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Journal of Virology, February 2000, p. 2038-2045, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Pathogenic Conversion of Live Attenuated Simian Immunodeficiency
Virus Vaccines Is Associated with Expression of Truncated Nef
Earl T.
Sawai,1,*
M. Sabry
Hamza,1
Michael
Ye,1
Karen E. S.
Shaw,2 and
Paul A.
Luciw1,2,*
Department of Medical
Pathology1 and Center for Comparative
Medicine,2 University of California, Davis,
California 95616
Received 21 May 1999/Accepted 18 November 1999
Rhesus macaques infected with simian immunodeficiency virus (SIV)
containing either a large nef deletion
(SIVmac239
152nef) 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.
*
Corresponding author. Mailing address for Earl T. Sawai: Department of Medical Pathology, University of California, One
Shields Ave., Davis, CA 95616. Phone: (530) 754-8873. Fax: (530)
752-4548. E-mail: etsawai{at}ucdavis.edu. Mailing address for
Paul A. Luciw: Center for Comparative Medicine, University of
California, Davis, One Shields Ave., Davis, CA 95616. Phone: (530)
752-3430. Fax: (530) 752-7914. E-mail: paluciw{at}ucdavis.edu.
Journal of Virology, February 2000, p. 2038-2045, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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