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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3602-3608. Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-03-1076. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1076v1 106/10/3602    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Silverman, L. R. Articles by Lairmore, M. D. Search for Related Content PubMed PubMed Citation Articles by Silverman, L. R. Articles by Lairmore, M. D. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations Lee R. Silverman, Andrew J. Phipps, Andy Montgomery, Soledad Fernandez, Tomonori Tsukahara, Lee Ratner, and Michael D. Lairmore From the Center for Retrovirus Research and Department of Veterinary Biosciences, the Center for Biostatistics, and the Comprehensive Cancer Center, The Arthur James Cancer Hospital and Research Institute, The Ohio State University, Columbus, OH; the Department of Microbiology and Immunology, Shinshu University School of Medicine, Nagano, Japan; and the Department of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St Louis, MO. Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell lymphoma/leukemia (ATL). The HTLV-1 envelope gene exhibits limited variability when examined from infected individuals, but has not been tested using infectious clones of the virus in animal models. In vitro assays indicate that HTLV-1 envelope (Env) Ser75Ile, Asn95Asp, and Asn195Asp surface unit (SU) mutants are able to replicate in and immortalize lymphocytes. Herein, we examined the effects of these Env mutants in rabbits inoculated with HTLV-1 immortalized ACH.75, ACH.95, or ACH.195 cell lines (expressing full-length molecular clones with the SU mutations) or the ACH.1 cell line (expressing wild-type SU). All rabbits became infected, and the fidelity of the mutations was maintained throughout the 8-week study. However, SU point mutations resulted in decreased antibody responses to viral group-associated antigen (Gag) and Env antigens. ACH.195 rabbits had a selective decreased antibody response to SU, and one ACH.195 rabbit had an antibody response to both HTLV-1 and HTLV-2 SUs. Some mutant inoculation groups had altered proviral loads. However, peripheral-blood mononuclear cell (PBMC) proviral loads did not correlate with antibody responses. Our data are the first to demonstrate that mutations in critical determinants of HTLV-1 Env SU altered antibody responses and proviral loads, but do not prevent viral replication in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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