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Journal of Virology, June 2003, p. 6855-6866, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6855-6866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Expression of Simian Immunodeficiency Virus (SIV) Nef in Astrocytes during Acute and Terminal Infection and Requirement of Nef for Optimal Replication of Neurovirulent SIV In Vitro

Emily D. Overholser, Gary D. Coleman, Jennifer L. Bennett, Rebecca J. Casaday, M. Christine Zink, Sheila A. Barber, and Janice E. Clements*

Department of Comparative Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287

Received 5 July 2002/ Accepted 18 March 2003

As the most numerous cells in the brain, astrocytes play a critical role in maintaining central nervous system homeostasis, and therefore, infection of astrocytes by human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) in vivo could have important consequences for the development of HIV encephalitis. In this study, we establish that astrocytes are infected in macaques during acute SIV infection (10 days postinoculation) and during terminal infection when there is evidence of SIV-induced encephalitis. Additionally, with primary adult rhesus macaque astrocytes in vitro, we demonstrate that the macrophage-tropic, neurovirulent viruses SIV/17E-Br and SIV/17E-Fr replicate efficiently in astrocytes, while the lymphocyte-tropic, nonneurovirulent virus SIVmac239 open-nef does not establish productive infection. Furthermore, aminoxypentane-RANTES abolishes virus replication, suggesting that these SIV strains utilize the chemokine receptor CCR5 for entry into astrocytes. Importantly, we show that SIV Nef is required for optimal replication in primary rhesus macaque astrocytes and that normalizing input virus by particle number rather than by infectivity reveals a disparity between the ability of a Nef-deficient virus and a virus encoding a nonmyristoylated form of Nef to replicate in these central nervous system cells. Since the myristoylated form of Nef has been implicated in functions such as CD4 and major histocompatibility complex I downregulation, kinase association, and enhancement of virion infectivity, these data suggest that an as yet unidentified function of Nef may exist to facilitate SIV replication in astrocytes that may have important implications for in vivo pathogenesis.

* Corresponding author. Mailing address: Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287. Phone: (410) 955-9770. Fax: (410) 955-9823. E-mail: jclement{at}jhmi.edu.

Journal of Virology, June 2003, p. 6855-6866, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6855-6866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Overholser, E. D., Babas, T., Zink, M. C., Barber, S. A., Clements, J. E. (2005). CD4-Independent Entry and Replication of Simian Immunodeficiency Virus in Primary Rhesus Macaque Astrocytes Are Regulated by the Transmembrane Protein. J. Virol. 79: 4944-4951 [Abstract] [Full Text]  
  • Strain, M. C., Letendre, S., Pillai, S. K., Russell, T., Ignacio, C. C., Gunthard, H. F., Good, B., Smith, D. M., Wolinsky, S. M., Furtado, M., Marquie-Beck, J., Durelle, J., Grant, I., Richman, D. D., Marcotte, T., McCutchan, J. A., Ellis, R. J., Wong, J. K. (2005). Genetic Composition of Human Immunodeficiency Virus Type 1 in Cerebrospinal Fluid and Blood without Treatment and during Failing Antiretroviral Therapy. J. Virol. 79: 1772-1788 [Abstract] [Full Text]  


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