RNA Modulates the Interaction Between Influenza A Virus NS1 and Human PABP1

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2018 May 22

PMID 29782795

Citations 7

Authors

Bryan H Arias-Mireles

Cyrus M de Rozieres

Kevin Ly

Simpson Joseph

Affiliations

Soon will be listed here.

Abstract

Nonstructural protein 1 (NS1) is a multifunctional protein involved in preventing host-interferon response in influenza A virus (IAV). Previous studies have indicated that NS1 also stimulates the translation of viral mRNA by binding to conserved sequences in the viral 5'-UTR. Additionally, NS1 binds to poly(A) binding protein 1 (PABP1) and eukaryotic initiation factor 4G (eIF4G). The interaction of NS1 with the viral 5'-UTR, PABP1, and eIF4G has been suggested to specifically enhance the translation of viral mRNAs. In contrast, we report that NS1 does not directly bind to sequences in the viral 5'-UTR, indicating that NS1 is not responsible for providing the specificity to stimulate viral mRNA translation. We also monitored the interaction of NS1 with PABP1 using a new, quantitative FRET assay. Our data show that NS1 binds to PABP1 with high affinity; however, the binding of double-stranded RNA (dsRNA) to NS1 weakens the binding of NS1 to PABP1. Correspondingly, the binding of PABP1 to NS1 weakens the binding of NS1 to double-stranded RNA (dsRNA). In contrast, the affinity of PABP1 for binding to poly(A) RNA is not significantly changed by NS1. We propose that the modulation of NS1·PABP1 interaction by dsRNA may be important for the viral cycle.

Citing Articles

Structural Investigations of Interactions between the Influenza a Virus NS1 and Host Cellular Proteins.

Blake M, Kleinpeter A, Jureka A, Petit C Viruses. 2023; 15(10).

PMID: 37896840 PMC: 10612106. DOI: 10.3390/v15102063.

Role of CIV NS1 Protein in Innate Immunity and Viral Replication.

Fu C, Zhu W, Cao N, Liu W, Lu Z, Wong Z Int J Mol Sci. 2023; 24(12).

PMID: 37373204 PMC: 10298371. DOI: 10.3390/ijms241210056.

Strategies of Influenza A Virus to Ensure the Translation of Viral mRNAs.

Li H, Yang C, Lo S Pathogens. 2022; 11(12).

PMID: 36558855 PMC: 9783940. DOI: 10.3390/pathogens11121521.

Interaction of the Influenza A Virus NS1 Protein with the 5'-m7G-mRNA·eIF4E·eIF4G1 Complex.

Cruz A, Joseph S Biochemistry. 2022; 61(14):1485-1494.

PMID: 35797022 PMC: 10164398. DOI: 10.1021/acs.biochem.2c00019.

Influenza A Virus NS1 Protein Binds as a Dimer to RNA-Free PABP1 but Not to the PABP1·Poly(A) RNA Complex.

de Rozieres C, Joseph S Biochemistry. 2020; 59(46):4439-4448.

PMID: 33172261 PMC: 8034803. DOI: 10.1021/acs.biochem.0c00666.

References

Deo R, Bonanno J, Sonenberg N, Burley S . Recognition of polyadenylate RNA by the poly(A)-binding protein. Cell. 1999; 98(6):835-45. DOI: 10.1016/s0092-8674(00)81517-2. View

Desselberger U, Racaniello V, Zazra J, Palese P . The 3' and 5'-terminal sequences of influenza A, B and C virus RNA segments are highly conserved and show partial inverted complementarity. Gene. 1980; 8(3):315-28. DOI: 10.1016/0378-1119(80)90007-4. View

Panthu B, Terrier O, Carron C, Traversier A, Corbin A, Balvay L . The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs. J Mol Biol. 2017; 429(21):3334-3352. DOI: 10.1016/j.jmb.2017.04.007. View

Park Y, Katze M . Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J Biol Chem. 1995; 270(47):28433-9. DOI: 10.1074/jbc.270.47.28433. View

Wong I, Lohman T . A double-filter method for nitrocellulose-filter binding: application to protein-nucleic acid interactions. Proc Natl Acad Sci U S A. 1993; 90(12):5428-32. PMC: 46733. DOI: 10.1073/pnas.90.12.5428. View

Tsai P, Chiou N, Kuss S, Garcia-Sastre A, Lynch K, Fontoura B . Cellular RNA binding proteins NS1-BP and hnRNP K regulate influenza A virus RNA splicing. PLoS Pathog. 2013; 9(6):e1003460. PMC: 3694860. DOI: 10.1371/journal.ppat.1003460. View

Cassetti M, Noah D, Montelione G, KRUG R . Efficient translation of mRNAs in influenza A virus-infected cells is independent of the viral 5' untranslated region. Virology. 2001; 289(2):180-5. DOI: 10.1006/viro.2001.1149. View

Kainov D, Muller K, Theisen L, Anastasina M, Kaloinen M, Muller C . Differential effects of NS1 proteins of human pandemic H1N1/2009, avian highly pathogenic H5N1, and low pathogenic H5N2 influenza A viruses on cellular pre-mRNA polyadenylation and mRNA translation. J Biol Chem. 2010; 286(9):7239-47. PMC: 3044980. DOI: 10.1074/jbc.M110.203489. View

Rodriguez A, Perez-Gonzalez A, Nieto A . Influenza virus infection causes specific degradation of the largest subunit of cellular RNA polymerase II. J Virol. 2007; 81(10):5315-24. PMC: 1900203. DOI: 10.1128/JVI.02129-06. View

10.

Enami K, Sato T, Nakada S, ENAMI M . Influenza virus NS1 protein stimulates translation of the M1 protein. J Virol. 1994; 68(3):1432-7. PMC: 236597. DOI: 10.1128/JVI.68.3.1432-1437.1994. View

11.

Salvatore M, Basler C, Parisien J, Horvath C, Bourmakina S, Zheng H . Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis. J Virol. 2002; 76(3):1206-12. PMC: 135795. DOI: 10.1128/jvi.76.3.1206-1212.2002. View

12.

KRUG R, Morgan M, Shatkin A . Influenza viral mRNA contains internal N6-methyladenosine and 5'-terminal 7-methylguanosine in cap structures. J Virol. 1976; 20(1):45-53. PMC: 354964. DOI: 10.1128/JVI.20.1.45-53.1976. View

13.

Eschenfeldt W, Maltseva N, Stols L, Donnelly M, Gu M, Nocek B . Cleavable C-terminal His-tag vectors for structure determination. J Struct Funct Genomics. 2010; 11(1):31-9. PMC: 2885959. DOI: 10.1007/s10969-010-9082-y. View

14.

Katze M, DeCorato D, KRUG R . Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus. J Virol. 1986; 60(3):1027-39. PMC: 253342. DOI: 10.1128/JVI.60.3.1027-1039.1986. View

15.

Chen E, Sharma M, Shi X, Agrawal R, Joseph S . Fragile X mental retardation protein regulates translation by binding directly to the ribosome. Mol Cell. 2014; 54(3):407-417. PMC: 4019695. DOI: 10.1016/j.molcel.2014.03.023. View

16.

de la Luna S, Fortes P, Beloso A, Ortin J . Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs. J Virol. 1995; 69(4):2427-33. PMC: 188917. DOI: 10.1128/JVI.69.4.2427-2433.1995. View

17.

Chen Z, Li Y, KRUG R . Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery. EMBO J. 1999; 18(8):2273-83. PMC: 1171310. DOI: 10.1093/emboj/18.8.2273. View

18.

Eschenfeldt W, Lucy S, Millard C, Joachimiak A, Mark I . A family of LIC vectors for high-throughput cloning and purification of proteins. Methods Mol Biol. 2008; 498:105-15. PMC: 2771622. DOI: 10.1007/978-1-59745-196-3_7. View

19.

Aragon T, de la Luna S, Novoa I, Carrasco L, Ortin J, Nieto A . Eukaryotic translation initiation factor 4GI is a cellular target for NS1 protein, a translational activator of influenza virus. Mol Cell Biol. 2000; 20(17):6259-68. PMC: 86100. DOI: 10.1128/MCB.20.17.6259-6268.2000. View

20.

Bier K, York A, Fodor E . Cellular cap-binding proteins associate with influenza virus mRNAs. J Gen Virol. 2011; 92(Pt 7):1627-1634. DOI: 10.1099/vir.0.029231-0. View