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
Google Scholar
Right arrow Articles by Taylor, J. M.
Right arrow Articles by Nicot, C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taylor, J. M.
Right arrow Articles by Nicot, C.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 11467-11476, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00952-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Novel Role for Interleukin-2 Receptor-Jak Signaling in Retrovirus Transmission{triangledown}

J. M. Taylor,1 M. Brown,1 M. Nejmeddine,3 K. J. Kim,2 L. Ratner,4 M. Lairmore,5 and C. Nicot1*

University of Kansas Medical Center, Department of Pathology and Laboratory Medicine,1 Department of Microbiology, Molecular Genetics, and Immunology, 3025 Wahl Hall West, 3901 Rainbow Blvd., Kansas City, Kansas 66160,2 Department of Immunology, Wright-Fleming Institute Imperial College, London W2 1PG, United Kingdom,3 Division of Molecular Oncology, Washington University, 660 South Euclid Ave., St. Louis, Missouri 63110,4 Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 432105

Received 13 May 2009/ Accepted 24 August 2009

Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma, and it encodes a number of nonstructural proteins that are involved in virus replication and immune evasion. The viral protein p12 previously has been characterized to interfere with major histocompatibility complex class, ICAM-1, and ICAM-2 expression, and it activates STAT5. Using a previously established T-cell line immortalized with an HTLV-1 molecular clone deleted for p12, we assessed the role of p12 in regulating cellular growth and virus transmission. These cells were complemented for p12 expression by the transduction of a lentivirus vector expressing p12. We report that p12 conferred a selective growth advantage in vitro and increased the colony formation of human T cells in soft-agar assays. Consistently with previous studies, p12– and p12+ cell lines produced similar amounts of virus particles released into the supernatant of cultured cells, although we found that p12 expression greatly enhanced virus transmission. Moreover, we found that interleukin-2 (IL-2) stimulation also increased HTLV-1 transmission whether p12 was expressed or not, and inversely, that the inhibition of Jak signaling significantly reduced HTLV-1 transmission. Intriguingly, IL-2/Jak signaling was not associated with changes in viral gene expression, viral RNA encapsidation, the maturation of the virus particle, cell-cell adherence, or Gag polarization and virological synapse formation. We do demonstrate, however, that IL-2 stimulation and p12 expression significantly increased the rate of syncytium formation, revealing a novel role for IL-2 signaling and Jak activation in HTLV-1 virus transmission.

* Corresponding author. Mailing address: University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, MSN 3045, 3901 Rainbow Blvd., Kansas City, KS 66160. Phone: (913) 588-6724. Fax: (913) 945-6836. E-mail: cnicot{at}kumc.edu

{triangledown} Published ahead of print on 2 September 2009.

Journal of Virology, November 2009, p. 11467-11476, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00952-09
Copyright © 2009, 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»