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Journal of Virology, February 2005, p. 1361-1366, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1361-1366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Rearrangement of Simian Virus 40 Regulatory Region Is Not Required for Induction of Progressive Multifocal Leukoencephalopathy in Immunosuppressed Rhesus Monkeys

Xin Dang,1 Michael K. Axthelm,2,3 Norman L. Letvin,1 and Igor J. Koralnik1,4*

Division of Viral Pathogenesis,1 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,4 Vaccine and Gene Therapy Institute,2 Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon3

Received 25 June 2004/ Accepted 14 September 2004

Rearrangements of the JC virus (JCV) regulatory region (RR) are consistently found in the brains of patients with progressive multifocal leukoencephalopathy (PML), whereas the archetype RR is present in their kidneys. In addition, the C terminus of the large T antigen (T-Ag) shows greater variability in PML than does the rest of the coding region. To determine whether similar changes in simian virus 40 (SV40) are necessary for disease induction in monkeys, we sequenced the SV40 RR and the C terminus of the T-Ag from the brain of simian/human immunodeficiency virus (SHIV)-infected monkey 18429, which presented spontaneously with an SV40-associated PML-like disease, as well as from the peripheral blood mononuclear cells (PBMC), kidneys, and brains of SV40-seronegative, SHIV-infected monkeys 21289 and 21306, which were inoculated with the 18429 brain SV40 isolate. These animals developed both SV40-associated PML and meningoencephalitis. Thirteen types of SV40 RR were characterized. Compared to the SV40 archetype, we identified RRs with variable deletions in either the origin of replication, the 21-bp repeat elements, or the late promoter, as well as deletions or duplications of the 72-bp enhancer. The archetype was the most prominent RR in the brain of monkey 18429. Shortly after inoculation, a wide range of RRs could be found in the PBMC of monkeys 21289 and 21306. However, the archetype RR became the predominant type in their blood, kidneys, and brains at the time of sacrifice. On the contrary, the T-Ag C termini remained identical in all compartments of the three animals. These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, RE-213, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-1568. Fax: (617) 667-8210. E-mail: ikoralni{at}bidmc.harvard.edu.

Journal of Virology, February 2005, p. 1361-1366, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1361-1366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sroller, V., Vilchez, R. A., Stewart, A. R., Wong, C., Butel, J. S. (2008). Influence of the Viral Regulatory Region on Tumor Induction by Simian Virus 40 in Hamsters. J. Virol. 82: 871-879 [Abstract] [Full Text]  


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