Alpha interferon enhances TRIM5alpha-mediated antiviral activities in human and rhesus monkey cells.
Dominant, constitutively expressed antiretroviral factors, including TRIM5alpha and APOBEC3 proteins, are distinguished from the conventional innate immune systems and are classified as intrinsic immunity factors. Here, we demonstrate that interferon alpha (IFN-alpha) treatment upregulates TRIM5alpha mRNA in rhesus monkey cells, which correlates with the enhanced TRIM5alpha-mediated pre- and postintegration blocks of human immunodeficiency virus replication. In human cells, IFN-alpha increases the levels of TRIM5alpha mRNA, resulting in enhanced antiviral activity against N-tropic murine leukemia virus infection. These observations indicate that the TRIM5alpha-mediated antiviral effects can be orchestrated by the conventional innate immune response. It is conceivable that TRIM5alpha plays an essential role in controlling both the initial retroviral exposure and the subsequent viral dissemination in vivo.
Sakuma
Ryuta
R
Molecular Medicine Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Mael
Amber A
AA
Ikeda
Yasuhiro
Y
D000071478:APOBEC Deaminases; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D002460:Cell Line; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D016898:Interferon-alpha / Q000494:pharmacology*; D009052:Leukemia Virus, Murine / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D016898:Interferon-alpha; D011506:Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase