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Journal of Virology, November 1998, p. 8841-8851, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Isolation and Characterization of a Neuropathogenic Simian Immunodeficiency Virus Derived from a Sooty Mangabey

Francis J. Novembre,1,2,* Juliette De Rosayro,1 Shawn P. O'Neil,2,3 Daniel C. Anderson,3 Sherry A. Klumpp,3 and Harold M. McClure3,4

Divisions of Microbiology and Immunology1 and Research Resources,3 Yerkes Regional Primate Research Center, and Departments of Microbiology and Immunology2 and Pathology,4 School of Medicine, Emory University, Atlanta, Georgia 30322

Received 4 May 1998/Accepted 10 August 1998

Transfusion of blood from a simian immunodeficiency virus (SIV)- and simian T-cell lymphotropic virus-infected sooty mangabey (designated FGb) to rhesus and pig-tailed macaques resulted in the development of neurologic disease in addition to AIDS. To investigate the role of SIV in neurologic disease, virus was isolated from a lymph node of a pig-tailed macaque (designated PGm) and the cerebrospinal fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques. SIV-related neuropathogenic effects were observed in 100% of the pig-tailed macaques inoculated with either virus. Lesions in these animals included extensive formation of SIV RNA-positive giant cells in the brain parenchyma and meninges. Based upon morphology, the majority of infected cells in both lymphoid and brain tissue appeared to be of macrophage lineage. The virus isolates replicated very well in pig-tailed and rhesus macaque peripheral blood mononuclear cells (PBMC) with rapid kinetics. Differential replicative abilities were observed in both PBMC and macrophage populations, with viruses growing to higher titers in pig-tailed macaque cells than in rhesus macaque cells. An infectious molecular clone of virus derived from the isolate from macaque PGm (PGm5.3) was generated and was shown to have in vitro replication characteristics similar to those of the uncloned virus stock. While molecular analyses of this virus revealed its similarity to SIV isolates from sooty mangabeys, significant amino acid differences in Env and Nef were observed. This virus should provide an excellent system for investigating the mechanism of lentivirus-induced neurologic disease.

* Corresponding author. Mailing address: Yerkes Regional Primate Research Center, Emory University, 954 N. Gatewood Rd., Atlanta, GA 30322. Phone: (404) 727-7216. Fax: (404) 727-7845. E-mail: fnovembr{at}rmy.emory.edu.

Journal of Virology, November 1998, p. 8841-8851, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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