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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Coberley, C. R.
Right arrow Articles by Goodenow, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coberley, C. R.
Right arrow Articles by Goodenow, M. M.

 Previous Article  |  Next Article 

Journal of Virology, November 2004, p. 11477-11486, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11477-11486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Impact on Genetic Networks in Human Macrophages by a CCR5 Strain of Human Immunodeficiency Virus Type 1

Carter R. Coberley,1 James J. Kohler,1,2 Joseph N. Brown,1 Joseph T. Oshier,1 Henry V. Baker,2,3 Michael P. Popp,2,4 John W. Sleasman,5 and Maureen M. Goodenow1,2,6*

Departments of Pathology, Immunology, and Laboratory Medicine,1 Department of Pediatrics, Division of Immunology and Infectious Diseases,6 Department of Molecular Genetics and Microbiology, University of Florida College of Medicine,3 Interdisciplinary Center for Biotechnology Research,4 University of Florida Shands Cancer Center, Gainesville,2 All Children's Hospital, University of South Florida, St. Petersburg, Florida5

Received 2 March 2004/ Accepted 24 June 2004

Human immunodeficiency virus type 1 (HIV-1) impacts multiple lineages of hematopoietic cells, including lymphocytes and macrophages, either by direct infection or indirectly by perturbations of cell networks, leading to generalized immune deficiency. We designed a study to discover, in primary human macrophages, sentinel genetic targets that are impacted during replication over the course of 7 days by a CCR5-using virus. Expression of mRNA and proteins in virus- or mock-treated macrophages from multiple donors was evaluated. Hierarchical agglomerative cluster analysis grouped into distinct temporal expression patterns >900 known human genes that were induced or repressed at least fourfold by virus. Expression of more than one-third of the genes was induced rapidly by day 2 of infection, while other genes were induced at intermediate (day 4) or late (day 7) time points. More than 200 genes were expressed exclusively in either virus- or mock-treated macrophage cultures, independent of the donor, providing an unequivocal basis to distinguish an effect by virus. HIV-1 altered levels of mRNA and/or protein for diverse cellular programs in macrophages, including multiple genes that can contribute to a transition in the cell cycle from G1 to G2/M, in contrast to expression in mock-treated macrophages of genes that maintain G0/G1. Virus treatment activated mediators of cell cycling, including PP2A, which is impacted by Vpr, as well as GADD45 and BRCA1, potentially novel targets for HIV-1. The results identify interrelated programs conducive to optimal HIV-1 replication and expression of genes that can contribute to macrophage dysfunction.

* Corresponding author. Mailing address: Department of Pathology, Immunology, and Laboratory Medicine, Box 100275, University of Florida College of Medicine, 1600 S.W. Archer Rd., Gainesville, FL 32610. Phone: (352) 392-3429. Fax: (352) 392-0481. E-mail: goodenow{at}ufl.edu.

Journal of Virology, November 2004, p. 11477-11486, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11477-11486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Harman, A. N., Kraus, M., Bye, C. R., Byth, K., Turville, S. G., Tang, O., Mercier, S. K., Nasr, N., Stern, J. L., Slobedman, B., Driessen, C., Cunningham, A. L. (2009). HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. Blood 114: 85-94 [Abstract] [Full Text]  
  • Giri, M. S., Nebozyhn, M., Raymond, A., Gekonge, B., Hancock, A., Creer, S., Nicols, C., Yousef, M., Foulkes, A. S., Mounzer, K., Shull, J., Silvestri, G., Kostman, J., Collman, R. G., Showe, L., Montaner, L. J. (2009). Circulating Monocytes in HIV-1-Infected Viremic Subjects Exhibit an Antiapoptosis Gene Signature and Virus- and Host-Mediated Apoptosis Resistance. J. Immunol. 182: 4459-4470 [Abstract] [Full Text]  
  • Wahl, S. M., Greenwell-Wild, T., Vazquez, N. (2006). HIV accomplices and adversaries in macrophage infection. J. Leukoc. Biol. 80: 973-983 [Abstract] [Full Text]  
  • Giri, M. S., Nebozhyn, M., Showe, L., Montaner, L. J. (2006). Microarray data on gene modulation by HIV-1 in immune cells: 2000-2006. J. Leukoc. Biol. 80: 1031-1043 [Abstract] [Full Text]  
  • Ghaffari, G., Tuttle, D. L., Briggs, D., Burkhardt, B. R., Bhatt, D., Andiman, W. A., Sleasman, J. W., Goodenow, M. M. (2005). Complex Determinants in Human Immunodeficiency Virus Type 1 Envelope gp120 Mediate CXCR4-Dependent Infection of Macrophages. J. Virol. 79: 13250-13261 [Abstract] [Full Text]  


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