Novel role for interleukin-2 receptor-jak signaling in retrovirus transmission

J. M. Taylor, M. Brown, M. Nejmeddine, K. J. Kim, L. Ratner, Michael Dale Lairmore, C. Nicot

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11467-11476
Number of pages10
JournalJournal of Virology
Volume83
Issue number22
DOIs
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Taylor, J. M., Brown, M., Nejmeddine, M., Kim, K. J., Ratner, L., Lairmore, M. D., & Nicot, C. (2009). Novel role for interleukin-2 receptor-jak signaling in retrovirus transmission. Journal of Virology, 83(22), 11467-11476. https://doi.org/10.1128/JVI.00952-09