HIV-1 Nef protein in the nucleus influences adipogenesis as well as viral transcription through the peroxisome proliferator-activated receptors.
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.
Otake
Kaori
K
Nagoya University Hospital, Japan.
Omoto
Shinya
S
Yamamoto
Takuya
T
Okuyama
Harumi
H
Okada
Hidechika
H
Okada
Noriko
N
Kawai
Masahiro
M
Saksena
Nitin K
NK
Fujii
Yoichi R
YR
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
D005227:Fatty Acids; D015693:Gene Products, nef; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D054311:nef Gene Products, Human Immunodeficiency Virus