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Journal of Virology, August 1999, p. 6460-6467, Vol. 73, No. 8
Basic Research Laboratory, National Cancer
Institute, Bethesda, Maryland 20892,1 and
Instituto Nacional do Cancer, Rio de Janeiro,
Brazil2
Received 3 February 1999/Accepted 23 April 1999
The HTLV-1 singly spliced open reading frame I protein,
p12I, is highly unstable and appears to be necessary for
persistent infection in rabbits. Here we demonstrate that
p12I forms dimers through two putative leucine zipper
domains and that its stability is augmented by specific proteasome
inhibitors. p12I is ubiquitylated, and mutations of its
unique carboxy-terminus lysine residue to an arginine greatly enhance
its stability. Interestingly, analysis of 53 independent HTLV-1 strains
revealed that the natural p12I alleles found in ex vivo
samples of tropical spastic paraparesis-HTLV-1-associated myelopathy
patients contain a Lys at position 88 in some cases, whereas arginine
is consistently found at position 88 in HTLV-1 strains from all adult
T-cell leukemia-lymphoma (ATLL) cases and healthy carriers studied.
This apparent segregation of different alleles in tropical spastic
paraparesis-HTLV-associated myelopathy and ATLL or healthy carriers may
be relevant in vivo, since p12I binds the interleukin-2
receptor
0022-538X/99/$04.00+0
A Lysine-to-Arginine Change Found in Natural
Alleles of the Human T-Cell Lymphotropic/Leukemia Virus Type 1 p12I Protein Greatly Influences Its Stability

and
c chains, raising the possibility that
the two natural alleles might affect differently the regulation of
these molecules.
*
Corresponding author. Mailing address: National Cancer
Institute, 37 Convent Dr., Bldg. 37, Rm. 6A11, MSC 4255, Bethesda, MD
20892. Phone: (301) 496-2386. Fax: (301) 496-8394. E-mail: veffa{at}helix.nih.gov.
Present address: Division of Hematologic Oncology, Memorial
Sloan-Kettering Cancer Center, New York, NY 10021.
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