Signaling via the CD2 receptor enhances HTLV-1 replication in T lymphocytes.
Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of adult T cell leukemia/lymphoma and several chronic progressive immune-mediated diseases. Approximately 1-4% of infected individuals develop disease, generally decades following infection. Increased proviral transcription, mediated by the viral 40-kDa trans-activating protein, Tax, has been implicated in the pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains sequences responsive to cyclic AMP and protein kinase C, we hypothesized that lymphocyte activation signals initiated through the TCR/CD3 complex or CD2 receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate that mAbs directed against the CD2, but not the CD3 receptor increase viral p24 capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an immortalized HTLV-1 cell line. Consistent with transcriptional regulation, reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene construct under control of the HTLV-1 promoter. These data suggest a possible physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte activation may promote viral transcription in infected lymphocytes.
Guyot
D J
DJ
Center for Retrovirus Research and Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus 43210-1093, USA.
Newbound
G C
GC
Lairmore
M D
MD
D018801:CD2 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003432:Cross-Linking Reagents; D016356:Gene Products, tax / Q000235:genetics; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014162:Transfection; D014779:Virus Replication
D018801:CD2 Antigens; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D016356:Gene Products, tax; D012333:RNA, Messenger; D012367:RNA, Viral; D011971:Receptors, Immunologic; D015682:Retroviridae Proteins, Oncogenic; C060954:p24 protein, Human T-lymphotropic virus 1; D015500:Chloramphenicol O-Acetyltransferase