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Journal of Virology, July 2001, p. 6086-6094, Vol. 75, No. 13
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.6086-6094.2001
Free Major Histocompatibility Complex Class I Heavy Chain Is
Preferentially Targeted for Degradation by Human T-Cell
Leukemia/Lymphotropic Virus Type 1 p12I Protein
Julie M.
Johnson,1
Christophe
Nicot,1
Jake
Fullen,1
Vincenzo
Ciminale,2
Luca
Casareto,1
James C.
Mulloy,1,
Steve
Jacobson,3 and
Genoveffa
Franchini1,*
Basic Research Laboratory, National Cancer
Institute,1 and Viral Immunology
Section, National Institute of Neurological Disorders and
Stroke,3 Bethesda, Maryland 20892, and
Department of Oncology and Surgical Sciences, University of
Padova, Padova, Italy2
Received 22 September 2000/Accepted 23 March 2001
Human T-cell leukemia virus type 1 (HTLV-1) establishes a
persistent infection in the host despite a vigorous virus-specific immune response. Here we demonstrate that an HTLV-1-encoded protein, p12I, resides in the endoplasmic reticulum (ER) and Golgi
and physically binds to the free human major histocompatibility complex
class I heavy chains (MHC-I-Hc) encoded by the HLA-A2, -B7, and -Cw4 alleles. As a result of this interaction, the newly synthesized MHC-I-Hc fails to associate with
2-microglobulin and is
retrotranslocated to the cytosol, where it is degraded by the
proteasome complex. Targeting of the free MHC-I-Hc, and not the
MHC-I-Hc-
2-microglobulin complex, by p12I
represents a novel mechanism of viral interference and disrupts the
intracellular trafficking of MHC-I, which results in a significant decrease in surface levels of MHC-I on human T-cells. These findings suggest that the interaction of p12I with MHC-1-Hc may
interfere with antigen presentation in vivo and facilitate escape of
HTLV-1-infected cells from immune recognition.
*
Corresponding author. Mailing address: National Cancer
Institute, Basic Research Laboratory, 41 Library Dr., Bldg. 41, Rm. D804, MSC 5055, 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.
Journal of Virology, July 2001, p. 6086-6094, Vol. 75, No. 13
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.6086-6094.2001
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