This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Overholser, E. D.
Right arrow Articles by Clements, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Overholser, E. D.
Right arrow Articles by Clements, J. E.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4944-4951, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4944-4951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD4-Independent Entry and Replication of Simian Immunodeficiency Virus in Primary Rhesus Macaque Astrocytes Are Regulated by the Transmembrane Protein

Emily D. Overholser, Tahar Babas, M. Christine Zink, Sheila A. Barber, and Janice E. Clements*

The Retrovirus Laboratory, Department of Comparative Medicine and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland

Received 5 March 2004/ Accepted 1 December 2004

Previous studies have demonstrated that the genetic determinants of simian immunodeficiency virus (SIV) neurovirulence map to the env and nef genes. Recent studies from our laboratory demonstrated that SIV replication in primary rhesus macaque astrocyte cultures is dependent upon the nef gene. Here, we demonstrate that macrophage tropism is not sufficient for replication in astrocytes and that specific amino acids in the transmembrane (TM) portion of Env are also important for optimal SIV replication in astrocytes. Specifically, a Gly at amino acid position 751 and truncation of the cytoplasmic tail of TM are required for efficient replication in these cells. Studies using soluble CD4 demonstrated that these changes within the TM protein regulate CD4-independent, CCR5-dependent entry of virus into astrocytes. In addition, we observed that two distinct CD4-independent, neuroinvasive strains of SIV/DeltaB670 also replicated efficiently in astrocytes, further supporting the role of CD4 independence as an important determinant of SIV infection of astrocytes in vitro and in vivo.

* Corresponding author. Mailing address: Johns Hopkins University School of Medicine, 733 N. Broadway, 819 BRB, Baltimore, MD 21205. Phone: (410) 955-9770. Fax: (410) 955-9823. E-mail: jclement{at}jhmi.edu.

Journal of Virology, April 2005, p. 4944-4951, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4944-4951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»