Influenza virus activates human immunodeficiency virus type-1 gene expression in human CD4-expressing T cells through an NF-kappaB-dependent pathway.
Influenza virus infection can cause severe complications in human immunodeficiency virus type-1 (HIV-1)-infected individuals leading to an increased risk of complications and death compared to that seen in uninfected individuals. We assessed the capacity of influenza virus (Flu) to modulate transcription of the HIV-1 long terminal repeat (LTR) in human CD4+ T cells. We found that Flu is able to promote expression of both the transiently transfected and stably integrated HIV-1 LTR-driven reporter gene. Experiments performed with Arthrobacter-derived neuraminidase and ammonium chloride revealed that Flu-dependent activation of HIV-1 transcription required an intimate contact between Flu and the target cell and efficient entry of Flu inside human CD4+ T cells. Amplification of a Flu-specific mRNA by RT-PCR indicated that human T cells were indeed productively infected with Flu. Virus preparations rendered noninfectious after UV irradiation could no longer upregulate HIV-1 LTR activity. Furthermore, experiments conducted with wild type and NF-kappaB-mutated HIV-1 LTR-directed reporter vectors suggested that the positive action of Flu on HIV-1 LTR activity was mediated through the induction of NF-kappaB. Our data show that fully competent Flu can lead to NF-kappaB-dependent activation of HIV-1 transcription in CD4+ T cells.
Sun
Jiangfeng
J
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Bergeron
Marc
M
Barbeau
Benoit
B
Boivin
Guy
G
Tremblay
Michel J
MJ
D000643:Ammonium Chloride / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000276:immunology*; D009439:Neuraminidase / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection
D016328:NF-kappa B; D012367:RNA, Viral; D000643:Ammonium Chloride; D009439:Neuraminidase