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

20 Citations (Scopus)

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

Fingerprint

Retroviridae
Human T-lymphotropic virus 1
Interleukin-2 Receptors
interleukin-2
Interleukin-2
receptors
virus transmission
viruses
Viruses
T-lymphocytes
Virion
virion
T-Lymphocytes
Immune Evasion
Cell Line
Adult T Cell Leukemia Lymphoma
Lentivirus
cell lines
Viral Genes
immune evasion

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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

Novel role for interleukin-2 receptor-jak signaling in retrovirus transmission. / Taylor, J. M.; Brown, M.; Nejmeddine, M.; Kim, K. J.; Ratner, L.; Lairmore, Michael Dale; Nicot, C.

In: Journal of Virology, Vol. 83, No. 22, 11.2009, p. 11467-11476.

Research output: Contribution to journalArticle

Taylor, JM, Brown, M, Nejmeddine, M, Kim, KJ, Ratner, L, Lairmore, MD & Nicot, C 2009, 'Novel role for interleukin-2 receptor-jak signaling in retrovirus transmission', Journal of Virology, vol. 83, no. 22, pp. 11467-11476. https://doi.org/10.1128/JVI.00952-09
Taylor, J. M. ; Brown, M. ; Nejmeddine, M. ; Kim, K. J. ; Ratner, L. ; Lairmore, Michael Dale ; Nicot, C. / Novel role for interleukin-2 receptor-jak signaling in retrovirus transmission. In: Journal of Virology. 2009 ; Vol. 83, No. 22. pp. 11467-11476.
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