title: NF-κB inhibition facilitates the establishment of cell lines that chronically produce human T-lymphotropic virus type 1 viral particles.
abstract: Most human T-lymphotropic virus type 1 (HTLV-1)-infected HeLa and SupT1 cells cease proliferation and become senescent immediately after infection by HTLV-1 or transduction of the HTLV-1 tax gene. The cellular senescence response triggered by Tax is caused by hyperactivated NF-κB and mediated by cyclin-dependent kinase inhibitors, p21(CIP1/WAF1) and p27(KIP1). When NF-κB activity is blocked by a degradation-resistant form of IκBα, ΔN-IκBα, Tax-induced senescence is averted. Here, we show that NF-κB inhibition through the expression of ΔN-IκBα allows cells of a human osteosarcoma (HOS) cell line to be chronically infected by HTLV-1. Stable HTLV-1-producing HOS cell clones can be readily established and isolated. These clones continue to proliferate in culture; express Tax, Rex, Gag, and Env proteins persistently; and transmit HTLV-1 to naive HOS, SupT1, and Jurkat T reporter cell lines readily after cocultivation. As HOS cells are adherent to culture plates, infected T cells in suspension can be easily collected and characterized. The ease with which chronic and productive HTLV-1 infection can be established in cell culture through inhibition of NF-κB affords a useful means to examine in depth the molecular events of HTLV-1 replication and the mechanisms of action of viral genes.
  
  
  OBJECTIVE
  This paper describes a system for establishing cell lines that can be productively infected by human T-lymphotropic virus type 1 (HTLV-1) and can spread HTLV-1 to susceptible cells. Such a system can facilitate the study of HTLV-1 replication in cell culture.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Muhammad Atif
authors.initials: MA
authors.lastname: Zahoor
authors.forename: Subha
authors.initials: S
authors.lastname: Philip
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhi
authors.forename: Chou-Zen
authors.initials: CZ
authors.lastname: Giam
mesh_terms: D002460:Cell Line / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D049109:Cell Proliferation; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism; D014776:Virus Cultivation / Q000379:methods*; D014779:Virus Replication
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012191:Retroviridae Proteins; D000072000:NF-KappaB Inhibitor alpha