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Journal of Virology, April 2001, p. 4019-4022, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.4019-4022.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Suboptimal Nucleotides in the Infectious, Pathogenic Simian Immunodeficiency Virus Clone SIVmac239

Louis Alexander,1 Lynn Denekamp,2 Susan Czajak,2 and Ronald C. Desrosiers2,*

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520,1 and New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 017722

Received 30 October 2000/Accepted 12 January 2001

We analyzed virus sequences in two monkeys infected with SIVmac239 and two monkeys infected with SHIVnef that maintained high, persisting viral loads. Sequence changes were observed consistently at four loci in all four animals: a single nucleotide change in the Lys-tRNA primer binding site in the 5' long terminal repeat; two nucleotide changes that resulted in two amino acid changes in the pol gene product; and a single nucleotide change in the region of the simian immunodeficiency virus genome where the rev and env genes overlap, resulting in changes in the predicted amino acid sequences of both gene products. None of these mutations were seen in short-term cultures of CEM×174 cells infected with SIVmac239 or SHIVnef. At all four positions in all four animals, the new sequences represented consensus sequences for primate lentiviruses, whereas the inoculum sequences at these four loci have either never been or rarely been reported outside of SIVmac239. Thus, although cloned SIVmac239 is consistently pathogenic and consistently induces high viral load set points, it is clearly less than optimal at these four nucleotide positions.

* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., Southborough, MA 01772-9102. Phone: (508) 624-8042. Fax: (508) 624-8190. E-mail: ronald_desrosiers{at}hms.harvard.edu.

Journal of Virology, April 2001, p. 4019-4022, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.4019-4022.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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