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Journal of Virology, August 1999, p. 6460-6467, Vol. 73, No. 8
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

Raffaella Trovato,1 James C. Mulloy,1,dagger Julie M. Johnson,1 Shigeki Takemoto,1 Maria Pombo de Oliveira,2 and Genoveffa Franchini1,*

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 beta  and gamma 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.

dagger Present address: Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Journal of Virology, August 1999, p. 6460-6467, Vol. 73, No. 8
0022-538X/99/$04.00+0


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