Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of
adult T-cell leukiemia (ATL) and HTLV-1 associated myelopathy, also ca
lled tropical spastic paraparesis (HAM/TSP). Both clinical and in vitr
o evidence have demonstrated that the virus or its transactivator Tax,
are transforming, However, transformation appears to require addition
al, as yet poorly characterized, genetic changes in infected cells, JN
K is a recently characterized member of the MAP kinase family. Its sig
naling cascade is distinct from other members and has been demonstrate
d to play an important role in T-cell activation, at least partially t
hrough its downstream targets, c-jun and ATF-2. Here we demonstrate co
nstitutive activation of the JNK cascade in human lymphocytes transfor
med in vitro by HTLV-1 and also in Tax transformed murine fibroblasts.
Such activation is not induced by Tax expression alone, and occurs on
ly when infected lymphocytes become IL-2 independent or immortalized.
Constitutive JNK activation was also found in leukocytes isolated from
ATL patients. The acquisition of constitutive JNK activation may repr
esent an important later event in HTLV-1 tumorigenesis.