Human immunodeficiency virus type 1 (HIV-1) induces activation of multiple STATs in CD4+ cells of lymphocyte or monocyte/macrophage lineages
- 1 March 2003
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 73 (3), 407-416
- https://doi.org/10.1189/jlb.0702358
Abstract
Human immunodeficiency virus type 1 (HIV‐1) impacts the activation state of multiple lineages of hematopoietic cells. Chronic HIV‐1 infection among individuals with progressive disease can be associated with increased levels of activated signal transducers and activators of transcription (STATs) in peripheral blood mononuclear cells. To investigate interactions between HIV‐1 and CD4+ cells, activated, phosphorylated STAT proteins in nuclear extracts from lymphocytic and promonocytic cell lines as well as primary monocyte‐derived macrophages were measured. Levels of activated STATs increased six‐ to tenfold in HUT78 and U937 cells within 2 h following exposure to virions. The response to virus was dose‐dependent, but kinetics of activation was delayed relative to interleukin‐2 or interferon‐γ. Activation of STAT1, STAT3, and STAT5 occurred with diverse viral envelope proteins, independent of coreceptor use or viral replication. Envelope‐deficient virions had no effect on STAT activation. Monoclonal antibody engagement of CD4 identified a novel role for CD4 as a mediator in the activation of multiple STATs. Results provide a model for HIV‐1 pathogenesis in infected and noninfected hematopoietic cells.Keywords
Funding Information
- PHS (T32 CA09126, T32 AR07603, R01 HL58005, R01 HD32259, R01 AI47734)
- Elizabeth Glaser Pediatric AIDS Foundation (PG51154)
- American Lung Association Florida Seed and Young Investigator awards
- American Foundation for AIDS Research fellowship (70542–20-RFV)
- UF Shands Cancer Center, Interdisciplinary Center for Biotechnology Research
- Center for Mammalian Genetics, and Molecular Genetics and Microbiology core facilities
This publication has 63 references indexed in Scilit:
- T-cell subsets (Th1 versus Th2)Annals of Allergy, Asthma & Immunology, 2000
- JAKS AND STATS: Biological ImplicationsAnnual Review of Immunology, 1998
- Lymphocyte Activation in Health and DiseaseCritical Reviews in Immunology, 1997
- STATs: Signal Transducers and Activators of TranscriptionCell, 1996
- HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domainNature, 1990
- Qualitative Analysis of Immune Function in Patients with the Acquired Immunodeficiency SyndromeNew England Journal of Medicine, 1985
- Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis.JCI Insight, 1984
- Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factorThe Journal of Experimental Medicine, 1981
- Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5Journal of General Virology, 1977