This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiraragi, H. Articles by Lairmore, M. D. Search for Related Content PubMed PubMed Citation Articles by Hiraragi, H. Articles by Lairmore, M. D.

Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13^II Is Required for Viral Infectivity In Vivo

Hajime Hiraragi,^1, Seung-Jae Kim,¹ Andrew J. Phipps,¹ Micol Silic-Benussi,² Vincenzo Ciminale,² Lee Ratner,⁵ Patrick L. Green,^1,3,4 and Michael D. Lairmore^1,3,4*

Center for Retrovirus Research and Department of Veterinary Biosciences, College of Veterinary Medicine,¹ Comprehensive Cancer Center, The Arthur James Cancer Hospital and Solove Research Institute,³ Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio 43210,⁴ Department of Oncology and Surgical Sciences, University of Padova, Padova, 35128 Italy,² Department of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63130⁵

Received 14 October 2005/ Accepted 10 January 2006

Human T-lymphotropic virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia, encodes unique regulatory and accessory proteins in the pX region of the provirus, including the open reading frame II product p13^II. p13^II localizes to mitochondria, binds farnesyl pyrophosphate synthetase, an enzyme involved in posttranslational farnesylation of Ras, and alters Ras-dependent cell signaling and control of apoptosis. The role of p13^II in virus infection in vivo remains undetermined. Herein, we analyzed the functional significance of p13^II in HTLV-1 infection. We compared the infectivity of a human B-cell line that harbors an infectious molecular clone of HTLV-1 with a selective mutation that prevents the translation of p13^II (729.ACH.p13) to the infectivity of a wild-type HTLV-1-expressing cell line (729.ACH). 729.ACH and 729.ACH.p13 producer lines had comparable infectivities for cultured rabbit peripheral blood mononuclear cells (PBMC), and the fidelity of the start codon mutation in ACH.p13 was maintained after PBMC passage. In contrast, zero of six rabbits inoculated with 729.ACH.p13 cells failed to establish viral infection, whereas six of six rabbits inoculated with wild-type HTLV-1-expressing cells (729.ACH) were infected as measured by antibody responses, proviral load, and HTLV-1 p19 matrix antigen production from ex vivo-cultured PBMC. Our data are the first to indicate that the HTLV-1 mitochondrion-localizing protein p13^II has an essential biological role during the early phase of virus infection in vivo.

Present address: Genentech, Inc., MS68, 1 DNA Way, South San Francisco, CA 94080.

This article has been cited by other articles:

• Chevalier, S. A., Walic, M., Calattini, S., Mallet, A., Prevost, M.-C., Gessain, A., Mahieux, R. (2007). Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone. J. Virol. 81: 6276-6285 [Abstract] [Full Text]  
• Miyazato, P., Yasunaga, J.-i., Taniguchi, Y., Koyanagi, Y., Mitsuya, H., Matsuoka, M. (2006). De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common {gamma}-Chain Knockout Mice. J. Virol. 80: 10683-10691 [Abstract] [Full Text]