Novel role for interleukin-2 receptor-Jak signaling in retrovirus transmission.
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.
Taylor
J M
JM
University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, 3025 Wahl Hall West, 3901 Rainbow Blvd., Kansas City, Kansas 66160, USA.
Brown
M
M
Nejmeddine
M
M
Kim
K J
KJ
Ratner
L
L
Lairmore
M
M
Nicot
C
C
D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D053612:Janus Kinases / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015682:Retroviridae Proteins, Oncogenic; D050791:STAT Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; D053612:Janus Kinases