Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model

• Published in: Blood 2010-01, Vol.115 (4), p.815-823
• Main Authors: Haynes, Rashade A.H., Ware, Evan, Premanandan, Christopher, Zimmerman, Bevin, Yu, Lianbo, Phipps, Andrew J., Lairmore, Michael D.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD4-CD8 Ratio; Cyclosporine - blood; Cyclosporine - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Female; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - metabolism; Gene Products, env - genetics; Gene Products, env - metabolism; Hematologic and hematopoietic diseases; HTLV-I Infections - immunology; Human T-lymphotropic virus 1 - growth & development; Human T-lymphotropic virus 1 - immunology; Humans; Immunocompromised Host; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacology; Jurkat Cells; Lymphocytosis - immunology; Lymphocytosis - virology; Lymphoid Neoplasia; Lymphoma, T-Cell - virology; Medical sciences; Rabbits; Retroviridae Proteins, Oncogenic - genetics; Retroviridae Proteins, Oncogenic - metabolism; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - transplantation; T-Lymphocytes, Helper-Inducer - virology; Viral Load - drug effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-07-230912

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia and several lymphocyte-mediated inflammatory diseases. Persistent HTLV-1 infection is determined by a balance between host immune responses and virus spread. Immunomodulatory therapy involving HTLV-1–infected patients occurs in a variety of clinical settings. Knowledge of how these treatments influence host-virus relationships is not understood. In this study, we examined the effects of cyclosporine A (CsA)–induced immune suppression during early infection of HTLV-1. Twenty-four New Zealand white rabbits were split into 4 groups. Three groups were treated with either 10 or 20 mg/kg CsA or saline before infection. The fourth group was treated with 20 mg/kg CsA 1 week after infection. Immune suppression, plasma CsA concentration, ex vivo lymphocyte HTLV-1 p19 production, anti–HTLV-1 serologic responses, and proviral load levels were measured during infection. Our data indicated that CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1–infected rabbits, and altered long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Collectively, these data indicate immunologic control is a key determinant of early HTLV-1 spread and have important implications for therapeutic intervention during HTLV-1–associated diseases.