Affiliation:
1. From the Departments of Veterinary Biosciences and Molecular Virology Immunology, and Medical Genetics, Center for Retrovirus Research, Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH.
Abstract
Natural antisense viral transcripts have been recognized in retroviruses, including human T-cell leukemia virus type 1 (HTLV-1), HIV-1, and feline immunodeficiency virus (FIV), and have been postulated to encode proteins important for the infection cycle and/or pathogenesis of the virus. The antisense strand of the HTLV-1 genome encodes HBZ, a novel nuclear basic region leucine zipper (b-ZIP) protein that in overexpression assays down-regulates Tax oncoprotein-induced viral transcription. Herein, we investigated the contribution of HBZ to HTLV-1–mediated immortalization of primary T lymphocytes in vitro and HTLV-1 infection in a rabbit animal model. HTLV-1 HBZ mutant viruses were generated and evaluated for viral gene expression, protein production, and immortalization capacity. Biologic properties of HBZ mutant viruses in vitro were indistinguishable from wild-type HTLV-1, providing the first direct evidence that HBZ is dispensable for viral replication and cellular immortalization. Rabbits inoculated with irradiated cells expressing HTLV-1 HBZ mutant viruses became persistently infected. However, these rabbits displayed a decreased antibody response to viral gene products and reduced proviral copies in peripheral blood mononuclear cells (PBMCs) as compared with wild-type HTLV-1–infected animals. Our findings indicated that HBZ was not required for in vitro cellular immortalization, but enhanced infectivity and persistence in inoculated rabbits. This study demonstrates that retroviruses use negative-strand–encoded proteins in the establishment of chronic viral infections.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference42 articles.
1. Green PL, Chen ISY. Human T-cell leukemia virus types 1 and 2. In: Knipe DM, Howley P, Griffin D, Lamb R, Martin M, Straus S, eds. Virology. 4th ed. Philidelphia, PA: Lippincott Williams & Wilkins; 2001: 1941-1969.
2. Bartoe JT, Albrecht B, Collins ND, et al. Functional role of pX open reading frame II of human T-lymphotropic virus type 1 in maintenance of viral loads in vivo. J Virol. 2000;74: 1094-1100.
3. Collins ND, Newbound GC, Albrecht B, Beard J, Ratner L, Lairmore MD. Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo. Blood. 1998;91: 4701-4707.
4. Silverman LR, Phipps AJ, Montgomery A, Ratner L, Lairmore MD. Human T-cell lymphotropic virus type 1 open reading frame II-encoded p30II is required for in vivo replication: evidence of in vivo reversion. J Virol. 2004;78: 3837-3845.
5. Wycuff DR, Marriott SJ. The HTLV-1 Tax oncoprotein: hypertasking at the molecular level. Front Biosci. 2005;10: 620-642.
Cited by
161 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献