Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model.
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.
Haynes
Rashade A H
RA
Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, USA.
Ware
Evan
E
Premanandan
Christopher
C
Zimmerman
Bevin
B
Yu
Lianbo
L
Phipps
Andrew J
AJ
Lairmore
Michael D
MD
D000818:Animals; D016516:CD4-CD8 Ratio; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology*; D019169:Jurkat Cells; D008218:Lymphocytosis / Q000276:immunology / Q000821:virology; D016399:Lymphoma, T-Cell / Q000821:virology; D011817:Rabbits; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000637:transplantation / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
D015686:Gene Products, env; D007166:Immunosuppressive Agents; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C055266:gp46 protein, Human T-cell leukemia virus type I; C060955:p19 protein, Human T-lymphotropic virus 1; D016572:Cyclosporine