title: HIV-1 Nef protein in the nucleus influences adipogenesis as well as viral transcription through the peroxisome proliferator-activated receptors.
abstract: BACKGROUND
  Although the HIV-1 Nef protein (27 kDa) localizes primarily in cytoplasm, there is considerable evidence suggesting its occasional localization in the nucleus. Nef is known to play an important role in transcriptional events and viral replication, but the actual target of Nef in the nucleus remains to be identified.
  
  
  OBJECTIVE
  To examine the functional roles of Nef in the nucleus and its possible interactions with other unknown factors in the nucleus.
  
  
  METHODS
  High-density microarray analysis was used to screen directly the unique functions of Nef on host gene transcription. The nuclear localization of Nef and its effects on the expression of peroxisome proliferator-activated receptors (PPAR) was examined using PPAR promoter/reporter assay and immunoblotting. A long terminal repeat/reporter assay was used to investigated the effects of Nef and PPAR on viral transcription.
  
  
  RESULTS
  Nef in the nucleus suppressed PPAR gamma expression and reduced fatty acid levels in human T and macrophage cell lines. Expression of Nef or PPAR suppressed viral replication; the effect of PPAR gamma or retinoid X receptor-alpha on viral replication were reduced by coexpression of Nef in MT(-)4 T cells.
  
  
  CONCLUSIONS
  Nef may be involved in both viral replication and the wasting syndrome associated with AIDS.
authors.affiliation: Nagoya University Hospital, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Otake
authors.forename: Shinya
authors.initials: S
authors.lastname: Omoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Harumi
authors.initials: H
authors.lastname: Okuyama
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawai
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
authors.forename: Yoichi R
authors.initials: YR
authors.lastname: Fujii
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology*; D005227:Fatty Acids / Q000378:metabolism*; D015693:Gene Products, nef / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D005227:Fatty Acids; D015693:Gene Products, nef; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D054311:nef Gene Products, Human Immunodeficiency Virus