Using RNA-Seq, we examined the transcriptional response induced by each protein. Both IFN-ω4 and IFN-ω9 showed antiviral activity against RNA viruses, including MARV, with IFN-ω9 being more efficient than IFN-ω4. To probe the biological implications of this expansion, we synthesized IFN-ω4 and IFN-ω9 proteins and tested their antiviral activity in Egyptian rousette cells. A striking difference to the human genome is that Egyptian rousettes have an expanded repertoire of IFNW genes. In contrast to humans, these bats do not become sick when infected with MARV. Egyptian rousette bats ( Rousettus aegyptiacus) are the natural reservoir hosts of Marburg virus (MARV). While the mechanisms underlying this ability to avoid sickness are not known, deep sequencing studies of bat genomes have uncovered genetic adaptations that may have functional importance in the antiviral response of these animals. PMID 21471362.Bats host a number of viruses that cause severe disease in humans without experiencing overt symptoms of disease themselves. "Zipcode binding protein 1 regulates the development of dendritic arbors in hippocampal neurons". ^ Perycz M, Urbanska AS, Krawczyk PS, Parobczak K, Jaworski J (Apr 2011)."IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection". ^ Kuriakose T, Zheng M, Neale G, Kanneganti TD (February 2018)."Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis". ^ Zhang T, Yin C, Boyd DF, Quarato G, Ingram JP, Shubina M, et al."ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death". ^ a b Kesavardhana S, Kuriakose T, Guy CS, Samir P, Malireddi RK, Mishra A, Kanneganti TD (August 2017)."ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways". ^ Kuriakose T, Man SM, Subbarao Malireddi RK, Karki R, Kesavardhana S, Place DE, Neale G, Vogel P, Kanneganti TD (August 2016).Proceedings of the National Academy of Sciences of the United States of America. "The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA". ^ Ha SC, Kim D, Hwang HY, Rich A, Kim YG, Kim KK (Dec 2008).^ Rathinam VA, Fitzgerald KA (Mar 2011).^ a b "Entrez Gene: ZBP1 Z-DNA binding protein 1"."Complex regulation of the human gene for the Z-DNA binding protein DLM-1". ^ Rothenburg S, Schwartz T, Koch-Nolte F, Haag F (Feb 2002).National Center for Biotechnology Information, U.S. This protein is different from the nucleic acid sensor ZBP1.
Zipcode binding protein 1 (ZBP1) was shown to regulate dendritogenesis ( dendrite formation) in hippocampal neurons. A more recent study has identified transcription factor IRF1 as the upstream regulator of ZBP1 expression. Ī follow up study identified that ZBP1 senses the IAV ribonucleoprotein complex to induce cell death. However, recent investigation has found that ZBP1 is capable of sensing Z-form RNAs produced during IAV infection, cumulating in a form of caspase independent, inflammatory cell death called necroptosis.
Since DNA is not synthesized in any stage of IAV life cycle, DNA sensing playing a role in this context is unlikely. It has been found to sense Influenza A Virus (IAV) infection and induce cell death. The role of ZBP1 in DNA sensing has been questioned. DLM1 then binds to cytosolic Viral DNA using two Z-DNA-binding domains (Zα and Zβ) at its N-terminus along with a DNA binding domain (D3). Once ZBP1 is activated, it increases the production of antiviral cytokines such as interferon beta. DNA is normally contained in the nucleus of a cell, and therefore cells use proteins like ZBP1 as an indicator of a viral infection. Viral life cycles often include steps where DNA is exposed in the cytoplasm. ZBP1 recognizes DNA in the cytoplasm as an antiviral mechanism. Z-DNA formation is a dynamic process, largely controlled by the amount of supercoiling. ZBP1 is also an abbreviation for chicken or rat β-actin zipcode-binding protein 1, a homolog of the human insulin-like growth factor 2 mRNA-binding protein 1 ( IMP-1) and murine CRD-BP, the proteins involved in mRNA transport ( RNA-binding proteins, RBPs).ĭLM1 encodes a Z-DNA binding protein.
Z-DNA-binding protein 1, also known as DNA-dependent activator of IFN-regulatory factors ( DAI) and DLM-1, is a protein that in humans is encoded by the ZBP1 gene. positive regulation of type I interferon-mediated signaling pathway.regulation of type I interferon production.positive regulation of type I interferon production.