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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,dagger 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 beta 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-beta 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.

dagger 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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