Enhanced human T-cell lymphotropic virus type I expression following induction of the cellular stress response.
Human T-cell lymphotropic virus type I (HTLV-I) infection is typically associated with long incubation periods between virus exposure and disease manifestation. Although viral protein expression is considered to play an important role in the pathogenesis of HTLV-I-associated diseases, limited information is known regarding host cell mechanisms that control viral gene expression. This study was designed to evaluate modulation of HTLV-I gene expression following induction of the cellular stress response in HTLV-I-infected lymphocytes. The cellular stress response was elicited by treatment with either Na arsenite or thermal stress and was monitored by demonstrating increased expression of the 72-kDa heat shock protein. Induction of the cellular stress response in HTLV-I-infected lymphocytes resulted in significantly increased HTLV-I-mediated syncytia formation due to enhanced HTLV-I envelope (gp46) expression. Intracellular viral proteins and released p24 capsid protein were increased in stressed infected lymphocytes as compared to nonstressed infected lymphocytes. Furthermore, HTLV-I-LTR reporter gene constructs had increased activity (three- to sixfold) in a transiently transfected, uninfected lymphocyte cell line following induction of the cellular stress response. Quantitation of HTLV-I RNA expression by slot blot analysis of infected lymphocytes suggested variable increases in RNA accumulation. Northern blot analysis demonstrated no qualitative changes in expression of RNA species. These data suggest a relationship between modulation of viral replication and a basic cellular response to stress and have important implications for understanding host cell control mechanisms of HTLV-I expression.
Andrews
J M
JM
Department of Veterinary Biosciences, Ohio State University, Columbus 43210.
Oglesbee
M J
MJ
Trevino
A V
AV
Guyot
D J
DJ
Newbound
G C
GC
Lairmore
M D
MD
D018053:Arsenites / Q000494:pharmacology; D002459:Cell Fusion; D002461:Cell Line, Transformed; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology*; D015686:Gene Products, env / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins; D015486:HTLV-I Antigens / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000502:physiology; D017670:Sodium Compounds / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018053:Arsenites; D015686:Gene Products, env; D050884:HSP72 Heat-Shock Proteins; D015486:HTLV-I Antigens; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D017670:Sodium Compounds; C055266:gp46 protein, Human T-cell leukemia virus type I; C060954:p24 protein, Human T-lymphotropic virus 1; C017947:sodium arsenite