Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors.
Transcription of the human immunodeficiency virus (HIV)-1 is controlled by the cooperation of virally encoded and host regulatory proteins. The Tat protein is essential for viral replication, however, expression of Tat after virus entry requires HIV-1 promoter activation. A sequence in the 5' HIV-1 LTR, containing a binding site for transcription factors of the interferon regulatory factors (IRF) family has been suggested to be critical for HIV-1 transcription and replication. Here we show that IRF-1 activates HIV-1 LTR transcription in a dose-dependent fashion and in the absence of Tat. This has biological significance since IRF-1 is produced early upon virus entry, both in cell lines and in primary CD4+ T cells, and before expression of Tat. IRF-1 also cooperates with Tat in amplifying virus gene transcription and replication. This cooperation depends upon a physical interaction that is blocked by overexpression of IRF-8, the natural repressor of IRF-1, and, in turn is released by overexpression of IRF-1. These data suggest a key role of IRF-1 in the early phase of viral replication and/or during viral reactivation from latency, when viral transactivators are absent or present at very low levels, and suggest that the interplay between IRF-1 and IRF-8 may play a key role in virus latency.
Sgarbanti
Marco
M
Laboratory of Virology, Istituto Superiore di Sanità, 00161 Rome, Italy.
Borsetti
Alessandra
A
Moscufo
Nicola
N
Bellocchi
Maria C
MC
Ridolfi
Barbara
B
Nappi
Filomena
F
Marsili
Giulia
G
Marziali
Giovanna
G
Coccia
Eliana M
EM
Ensoli
Barbara
B
Battistini
Angela
A
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050835:Interferon Regulatory Factors; D019169:Jurkat Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099185:Interferon Regulatory Factor-8
D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050835:Interferon Regulatory Factors; D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099185:Interferon Regulatory Factor-8; C494257:IRF1 protein, human; C494229:IRF2 protein, human