Expression of IL-2 and IL-4 in T lymphocytes transformed by herpesvirus saimiri.
Herpesvirus saimiri (H. saimiri) is a highly oncogenic lymphotropic herpesvirus which can immortalize T lymphocytes and cause tumors in rabbits and New World monkeys. T cells infected with strain 484-77 of group C express four viral U-like small RNAs (HSUR1-4) and a 1.2-kb mRNA which encodes open reading frames ORF-1 and ORF-2. ORF-1 encodes a collagen-like oncoprotein. Deletion mutation analysis showed that ORF-1 and ORF-2 are essential for IL-2 independent growth of human T cells infected with H. saimiri. An earlier study also demonstrated that H. saimiri-immortalized cells carry functional IL-2 receptors. The work presented in this report investigated whether IL-2 and IL-4 is produced by H. saimiri-immortalized T lymphocytes. Both IL-2 mRNA and IL-4 mRNA were detected in various monkey T cells as well as human peripheral blood lymphocytes infected with wild-type H. saimiri. Secretion of IL-2 was suggested by cyclosporin A inhibition. IL-4 secretion by monkey T cell cultures was demonstrated by a bioassay and inhibition of bioactivity by an antibody to IL-4. The data also show that recombinant IL-4 stimulate H. saimiri-immortalized T cells; thus, IL-4 receptors are expressed. However, antibodies to human IL-4, IL-4 receptor, or soluble IL-4 receptor did not curtail growth of transformed cells. T cells infected with ORF-1 and ORF-2 deletion mutants expressed no detectable IL-2 mRNA. ORF-1, ORF-2, HSUR1, and HSUR2, were all essential for expression of IL-4 mRNA. These data are consistent with the hypothesis that H. saimiri-immortalized monkey and human T lymphocytes proliferate through autocrine secretion of IL-2 and that ORF-1, ORF-2, and HSUR sequences of the virus are involved in expression of lymphokines.
Chou
C S
CS
Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa 33612-4799, USA.
Medveczky
M M
MM
Geck
P
P
Vercelli
D
D
Medveczky
P G
PG
D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016572:Cyclosporine; D015967:Gene Expression Regulation, Viral; D000882:Haplorhini; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012342:RNA, Small Nuclear / Q000235:genetics; D017384:Sequence Deletion / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*
D007376:Interleukin-2; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; D015847:Interleukin-4; D016572:Cyclosporine