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Journal of Virology, July 1999, p. 6159-6165, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Persistent Infection of Rhesus Macaques by the Rev-Independent Nef(-) Simian Immunodeficiency Virus SIVmac239: Replication Kinetics and Genomic Stability

Agneta S. von Gegerfelt,1 Vladimir Liska,2,3 Nancy B. Ray,2,3 Harold M. McClure,4 Ruth M. Ruprecht,2,3 and Barbara K. Felber1,*

Human Retrovirus Pathogenesis Group, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 217021; Dana-Farber Cancer Institute2 and Department of Medicine,3 Harvard Medical School, Boston, Massachusetts 02115; and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 303224

Received 27 October 1998/Accepted 14 April 1999

We generated previously a Nef(-), replication-competent clone of SIVmac239 in which the Rev protein and the Rev-responsive element were replaced by the constitutive transport element (CTE) of simian retrovirus type 1 (A. S. von Gegerfelt and B. K. Felber, Virology 232:291-299, 1997). In the present report, we show that this virus was able to infect and replicate in rhesus macaques. The Rev-independent Nef(-) simian immunodeficiency virus induced a persistent humoral immune response in all monkeys, although viral loads were very low. Upon propagation in the monkeys, the genotype remained stable and the virus retained its in vitro growth characteristics. The infected monkeys showed normal hematological values and no signs of disease at more than 18 months post-virus exposure. Therefore, replacement of the essential Rev regulation by the CTE generated a virus variant that retained its replicative capacity both in vitro and in vivo, albeit at low levels.

* Corresponding author. Mailing address: ABL-Basic Research Program, Bldg. 535, Rm. 110, NCI-FCRDC, Frederick, MD 21702-1201. Phone: (301) 846-5159. Fax: (301) 846-7146. E-mail: felber{at}mail.ncifcrf.gov.

Journal of Virology, July 1999, p. 6159-6165, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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