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Filamentous versus Spherical Morphology: A Case Study of the Recombinant A/WSN/33 (H1N1) Virus

Published online by Cambridge University Press:  10 February 2020

Larisa V. Kordyukova*
Affiliation:
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991Moscow, Russia
Ramil R. Mintaev
Affiliation:
Mechnikov Research Institute of Vaccine and Sera, 105064Moscow, Russia Federal State Budgetary Institution «Center for Strategic Planning and Management for Medical and Biological Health Risks», Ministry of Health, 119121Moscow, Russia
Artyom A. Rtishchev
Affiliation:
Mechnikov Research Institute of Vaccine and Sera, 105064Moscow, Russia
Marina S. Kunda
Affiliation:
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health, 123098Moscow, Russia
Natalia N. Ryzhova
Affiliation:
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health, 123098Moscow, Russia
Sergei S. Abramchuk
Affiliation:
Department of Chemistry, Lomonosov Moscow State University, 119234Moscow, Russia A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 119991Moscow, Russia
Marina V. Serebryakova
Affiliation:
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991Moscow, Russia
Vladislav V. Khrustalev
Affiliation:
Department of General Chemistry, Belarusian State Medical University, 220116Minsk, Belarus
Tatyana A. Khrustaleva
Affiliation:
Biochemical Group of the Multidisciplinary Diagnostic Laboratory, Institute of Physiology of the National Academy of Sciences of Belarus, 220072Minsk, Belarus
Victor V. Poboinev
Affiliation:
Department of General Chemistry, Belarusian State Medical University, 220116Minsk, Belarus
Stanislav G. Markushin
Affiliation:
Mechnikov Research Institute of Vaccine and Sera, 105064Moscow, Russia
Olga L. Voronina
Affiliation:
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health, 123098Moscow, Russia
*
*Author for correspondence: Larisa V. Kordyukova, E-mail: kord@belozersky.msu.ru
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Abstract

Influenza A virus is a serious human pathogen that assembles enveloped virions on the plasma membrane of the host cell. The pleiomorphic morphology of influenza A virus, represented by spherical, elongated, or filamentous particles, is important for the spread of the virus in nature. Using fixative protocols for sample preparation and negative staining electron microscopy, we found that the recombinant A/WSN/33 (H1N1) (rWSN) virus, a strain considered to be strictly spherical, may produce filamentous particles when amplified in the allantoic cavity of chicken embryos. In contrast, the laboratory WSN strain and the rWSN virus amplified in Madin–Darby canine kidney cells exhibited a spherical morphology. Next-generation sequencing (NGS) suggested a rare Ser126Cys substitution in the M1 protein of rWSN, which was confirmed by the mass spectrometric analysis. No structurally relevant substitutions were found by NGS in other proteins of rWSN. Bioinformatics algorithms predicted a neutral structural effect of the Ser126Cys mutation. The mrWSN_M1_126S virus generated after the introduction of the reverse Cys126Ser substitution exhibited a similar host-dependent partially filamentous phenotype. We hypothesize that a shortage of some as-yet-undefined cellular components involved in virion budding and membrane scission may result in the appearance of filamentous particles in the case of usually “nonfilamentous” virus strains.

Type
Biological Applications
Copyright
Copyright © Microscopy Society of America 2020

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References

Al-Mubarak, F, Daly, J, Christie, D, Fountain, D & Dunham, SP (2015). Identification of morphological differences between avian influenza A viruses grown in chicken and duck cells. Virus Res 199, 919.CrossRefGoogle ScholarPubMed
Badham, MD & Rossman, JS (2016). Filamentous influenza viruses. Curr Clin Microbiol Rep 3, 155161.CrossRefGoogle ScholarPubMed
Baylor, NW, Li, Y, Ye, ZP & Wagner, RR (1988). Transient expression and sequence of the matrix (M1) gene of WSN influenza A virus in a vaccinia vector. Virology 163, 618621.CrossRefGoogle Scholar
Beale, R, Wise, H, Stuart, A, Ravenhill, BJ, Digard, P & Randow, F (2014). A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability. Cell Host Microbe 15, 239247.CrossRefGoogle ScholarPubMed
Bialas, KM, Bussey, KA, Stone, RL & Takimoto, T (2014). Specific nucleoprotein residues affect influenza virus morphology. J Virol 88, 22272234.CrossRefGoogle ScholarPubMed
Bourmakina, SV & García-Sastre, A (2003). Reverse genetics studies on the filamentous morphology of influenza A virus. J Gen Virol 84, 517527.CrossRefGoogle ScholarPubMed
Burleigh, LM, Calder, LJ, Skehel, JJ & Steinhauer, DA (2005). Influenza A viruses with mutations in the M1 helix six domain display a wide variety of morphological phenotypes. J Virol 79, 12621270.CrossRefGoogle ScholarPubMed
Calder, LJ, Wasilewski, S, Berriman, JA & Rosenthal, PB (2010). Structural organization of a filamentous influenza A virus. Proc Natl Acad Sci USA 107, 1068510690.CrossRefGoogle ScholarPubMed
Chen, BJ, Leser, GP, Morita, E & Lamb, RA (2007). Influenza virus hemagglutinin and neuraminidase, but not the matrix protein, are required for assembly and budding of plasmid-derived virus-like particles. J Virol 81, 71117123.CrossRefGoogle Scholar
Chiang, M-J, Musayev, FN, Kosikova, M, Lin, Z, Gao, Y, Mosier, PD, Althufairi, B, Ye, Z, Zhou, Q, Desai, UR, Xie, H & Safo, MK (2017). Maintaining pH-dependent conformational flexibility of M1 is critical for efficient influenza A virus replication. Emerg Microbes Infect 6, e108.CrossRefGoogle ScholarPubMed
Chlanda, P, Mekhedov, E, Waters, H, Sodt, A, Schwartz, C, Nair, V, Blank, PS & Zimmerberg, J (2017). Palmitoylation contributes to membrane curvature in influenza A virus assembly and hemagglutinin-mediated membrane fusion. J Virol 91. doi: 10.1128/JVI.00947-17.CrossRefGoogle ScholarPubMed
Chlanda, P, Schraidt, O, Kummer, S, Riches, J, Oberwinkler, H, Prinz, S, Kräusslich, H-G & Briggs, JAG (2015). Structural analysis of the roles of influenza A virus membrane-associated proteins in assembly and morphology. J Virol 89, 89578966.CrossRefGoogle ScholarPubMed
Choppin, PW, Murphy, JS & Tamm, I (1960). Studies of two kinds of virus particles which comprise influenza A2 virus strains. III. Morphological characteristics: Independence to morphological and functional traits. J Exp Med 112, 945952.CrossRefGoogle ScholarPubMed
Dadonaite, B, Vijayakrishnan, S, Fodor, E, Bhella, D & Hutchinson, EC (2016). Filamentous influenza viruses. J Gen Virol 97, 17551764.CrossRefGoogle ScholarPubMed
Dee, K (2017). Investigating Influenza A Virus Pleomorphy. Ireland: Trinity College Dublin.Google Scholar
Dou, D, Revol, R, Östbye, H, Wang, H & Daniels, R (2018). Influenza A virus cell entry, replication, virion assembly and movement. Front Immunol 9, 1581.CrossRefGoogle ScholarPubMed
Elleman, CJ & Barclay, WS (2004). The M1 matrix protein controls the filamentous phenotype of influenza A virus. Virology 321, 144153.CrossRefGoogle ScholarPubMed
Elton, D, Bruce, EA, Bryant, N, Wise, HM, MacRae, S, Rash, A, Smith, N, Turnbull, ML, Medcalf, L, Daly, JM & Digard, P (2013). The genetics of virus particle shape in equine influenza A virus. Influenza Other Respir Viruses 7(Suppl 4), 8189.CrossRefGoogle ScholarPubMed
Fletcher, K, Ulferts, R, Jacquin, E, Veith, T, Gammoh, N, Arasteh, JM, Mayer, U, Carding, SR, Wileman, T, Beale, R & Florey, O (2018). The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes. EMBO J 37, e97840.CrossRefGoogle ScholarPubMed
Hammer, Ø, Harper, DAT & Ryan, PD (2001). Paleontological statistics software package for education and data analysis. Palaeontol Electron 4, 9pp.Google Scholar
He, J, Sun, E, Bujny, MV, Kim, D, Davidson, MW & Zhuang, X (2013). Dual function of CD81 in influenza virus uncoating and budding. PLoS Pathog 9, e1003701.CrossRefGoogle ScholarPubMed
Hirst, JC & Hutchinson, EC (2019). Single-particle measurements of filamentous influenza virions reveal damage induced by freezing. J Gen Virol 100, 16311640.CrossRefGoogle ScholarPubMed
Hoffmann, E, Neumann, G, Kawaoka, Y, Hobom, G & Webster, RG (2000). A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 97, 61086113.CrossRefGoogle ScholarPubMed
Hoffmann, E, Stech, J, Guan, Y, Webster, RG & Perez, DR (2001). Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 146, 22752289.CrossRefGoogle ScholarPubMed
Hom, N, Gentles, L, Bloom, JD & Lee, KK (2019). Deep mutational scan of the highly conserved influenza A virus M1 matrix protein reveals substantial intrinsic mutational tolerance. J Virol 93, e00161-19.CrossRefGoogle ScholarPubMed
Hutchinson, EC, Charles, PD, Hester, SS, Thomas, B, Trudgian, D, Martínez-Alonso, M & Fodor, E (2014). Conserved and host-specific features of influenza virion architecture. Nat Commun 5, 4816.CrossRefGoogle ScholarPubMed
Ivanova, PT, Myers, DS, Milne, SB, McClaren, JL, Thomas, PG & Brown, HA (2015). Lipid composition of viral envelope of three strains of influenza virus—not all viruses are created equal. ACS Infect Dis 1, 399452.CrossRefGoogle Scholar
Jin, H, Leser, GP, Zhang, J & Lamb, RA (1997). Influenza virus hemagglutinin and neuraminidase cytoplasmic tails control particle shape. EMBO J 16, 12361247.CrossRefGoogle ScholarPubMed
Khrustalev, VV, Khrustaleva, TA & Poboinev, VV (2018). Amino acid content of beta strands and alpha helices depends on their flanking secondary structure elements. BioSystems 168, 4554.CrossRefGoogle ScholarPubMed
Kolesnikova, L, Heck, S, Matrosovich, T, Klenk, H-D, Becker, S & Matrosovich, M (2013). Influenza virus budding from the tips of cellular microvilli in differentiated human airway epithelial cells. J Gen Virol 94, 971976.CrossRefGoogle ScholarPubMed
Kordyukova, L, Krabben, L, Serebryakova, M & Veit, M (2019a). S-Acylation of proteins. Methods Mol Biol 1934, 265291.CrossRefGoogle Scholar
Kordyukova, LV & Serebryakova, MV (2012). Mass spectrometric approaches to study enveloped viruses: New possibilities for structural biology and prophylactic medicine. Biochemistry 77, 830842.Google ScholarPubMed
Kordyukova, LV, Serebryakova, MV, Polyakov, VY, Ovchinnikova, TV, Smirnova, YA, Fedorova, NV & Baratova, LA (2008). Influenza A virus M1 protein structure probed by in situ limited proteolysis with bromelain. Protein Pept Lett 15, 922930.CrossRefGoogle ScholarPubMed
Kordyukova, LV, Shtykova, EV, Baratova, LA, Svergun, DI & Batishchev, OV (2019b). Matrix proteins of enveloped viruses: A case study of Influenza A virus M1 protein. J Biomol Struct Dyn–690.CrossRefGoogle Scholar
Laemmli, UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680685.CrossRefGoogle ScholarPubMed
Mintaev, RR, Alexeevski, AV & Kordyukova, LV (2014). Co-evolution analysis to predict protein–protein interactions within influenza virus envelope. J Bioinform Comput Biol 12, 1441008.CrossRefGoogle ScholarPubMed
Mitnaul, LJ, Castrucci, MR, Murti, KG & Kawaoka, Y (1996). The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication. J Virol 70, 873879.CrossRefGoogle Scholar
Moulès, V, Terrier, O, Yver, M, Riteau, B, Moriscot, C, Ferraris, O, Julien, T, Giudice, E, Rolland, J-P, Erny, A, Bouscambert-Duchamp, M, Frobert, E, Rosa-Calatrava, M, Pu Lin, Y, Hay, A, Thomas, D, Schoehn, G & Lina, B (2011). Importance of viral genomic composition in modulating glycoprotein content on the surface of influenza virus particles. Virology 414, 5162.CrossRefGoogle ScholarPubMed
Nakatsu, S, Murakami, S, Shindo, K, Horimoto, T, Sagara, H, Noda, T & Kawaoka, Y (2018). Influenza C and D viruses package eight organized ribonucleoprotein complexes. J Virol 92, e02084-17.CrossRefGoogle Scholar
Noda, T (2011). Native morphology of influenza virions. Front Microbiol 2, 269.Google ScholarPubMed
Noda, T, Murakami, S, Nakatsu, S, Imai, H, Muramoto, Y, Shindo, K, Sagara, H & Kawaoka, Y (2018). Importance of the 1 + 7 configuration of ribonucleoprotein complexes for influenza A virus genome packaging. Nat Commun 9, 54.CrossRefGoogle ScholarPubMed
Pohl, MO, Lanz, C & Stertz, S (2016). Late stages of the influenza A virus replication cycle—a tight interplay between virus and host. J Gen Virol 97, 20582072.CrossRefGoogle Scholar
Ramírez, R & Marshall, SH (2018). Identification and isolation of infective filamentous particles in Infectious Salmon Anemia Virus (ISAV). Microb Pathog 117, 219224.CrossRefGoogle Scholar
Roberts, PC & Compans, RW (1998). Host cell dependence of viral morphology. Proc Natl Acad Sci USA 95, 57465751.CrossRefGoogle ScholarPubMed
Roberts, PC, Lamb, RA & Compans, RW (1998). The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation. Virology 240, 127137.CrossRefGoogle ScholarPubMed
Roberts, KL, Leser, GP, Ma, C & Lamb, RA (2013). The amphipathic helix of influenza A virus M2 protein is required for filamentous bud formation and scission of filamentous and spherical particles. J Virol 87, 99739982.CrossRefGoogle ScholarPubMed
Röper, K, Corbeil, D & Huttner, WB (2000). Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane. Nat Cell Biol 2, 582592.CrossRefGoogle ScholarPubMed
Rossman, JS, Jing, X, Leser, GP, Balannik, V, Pinto, LH & Lamb, RA (2010a). Influenza virus M2 ion channel protein is necessary for filamentous virion formation. J Virol 84, 50785088.CrossRefGoogle Scholar
Rossman, JS, Jing, X, Leser, GP & Lamb, RA (2010b). Influenza virus M2 protein mediates ESCRT-independent membrane scission. Cell 142, 902913.CrossRefGoogle Scholar
Rossman, JS & Lamb, RA (2011). Influenza virus assembly and budding. Virology 411, 229236.CrossRefGoogle ScholarPubMed
Rossman, JS, Leser, GP & Lamb, RA (2012). Filamentous influenza virus enters cells via macropinocytosis. J Virol 86, 1095010960.CrossRefGoogle ScholarPubMed
Safo, MK, Musayev, FN, Mosier, PD, Zhou, Q, Xie, H & Desai, UR (2014). Crystal structures of influenza A virus matrix protein M1: Variations on a theme. PLoS One 9, e109510.CrossRefGoogle ScholarPubMed
Sakai, T, Takagi, H, Muraki, Y & Saito, M (2018). Unique directional motility of influenza C virus controlled by its filamentous morphology and short-range motions. J Virol 92, e01522-17.CrossRefGoogle Scholar
Sanjana, NE, Cong, L, Zhou, Y, Cunniff, MM, Feng, G & Zhang, F (2012). A transcription activator-like effector toolbox for genome engineering. Nat Protoc 7, 171192.CrossRefGoogle ScholarPubMed
Seladi-Schulman, J, Steel, J & Lowen, AC (2013). Spherical influenza viruses have a fitness advantage in embryonated eggs, while filament-producing strains are selected in vivo. J Virol 87, 1334313353.CrossRefGoogle ScholarPubMed
Shaw, ML, Stone, KL, Colangelo, CM, Gulcicek, EE & Palese, P (2008). Cellular proteins in influenza virus particles. PLoS Pathog 4, e1000085.CrossRefGoogle ScholarPubMed
Simpson-Holley, M, Ellis, D, Fisher, D, Elton, D, McCauley, J & Digard, P (2002). A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions. Virology 301, 212225.CrossRefGoogle ScholarPubMed
Vijayakrishnan, S, Loney, C, Jackson, D, Suphamungmee, W, Rixon, FJ & Bhella, D (2013). Cryotomography of budding influenza A virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end. PLoS Pathog 9, e1003413.CrossRefGoogle ScholarPubMed
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