Membrane‐Containing Bacteriophages


Viruses exhibit vast diversity in their form and function and are by far the most numerous (estimates 1030–1032) organisms on earth. The largest group among viruses is bacteriophages (phages), the viruses that infect bacteria, with over 6000 identified members. Vast majority of the phages are composed of protein and nucleic acid with a head–tail morphology. Polyhedral, filamentous or pleomorphic phages comprise only less than 4% of the described bacteriophages, and a minority of these has lipid constituents in addition to nucleic acid and protein. These membrane‐containing bacteriophages form a diverse group of viruses and the major virus morphotypes are represented by the members of the virus families , and . The lipids as a bilayer can either form the outermost layer of the virion or be enclosed within the virus capsid. In both cases, the viral membranes are involved in cell entry processes.

Key Concepts

  • Membrane‐containing bacteriophages are a diverse group of bacterial viruses.
  • Bacteriophages with a membrane are usually sensitive to organic solvents and detergents.
  • Lipids in the viral membrane have a bilayer structure.
  • The virion proteins are all virus specific, but lipids are derived from host cytoplasmic membrane.
  • During virus morphogenesis, the virus‐specific membrane proteins exclude host proteins during formation of the viral membrane.
  • The viral protein‐rich membranes have an essential role during entry mediating the translocation of the genome across the bacterial cell envelopes.

Keywords: bacterial virus; lipid‐containing bacteriophage; membrane‐containing bacteriophage; virus evolution; life cycle

Figure 1. Morphotypes of the membrane‐containing bacteriophages. The type species of the membrane‐containing bacteriophage families and unassigned phages P23‐77, icosahedral phage 1 (SSIP‐1) and L172 are drawn to scale (Bar is 100 nm). Protein (blue), lipid bilayer (orange), DNA (purple) and RNA (red) are coloured. Double‐stranded and single‐stranded genomes are indicated by double and single lines, respectively.
Figure 2. Corticovirus PM2. A schematic presentation of the virion architecture and functions of the proteins.
Figure 3. Tectivirus PRD1. (Upper panel) A schematic presentation of the PRD1 virion architecture and functions of the proteins. (Lower panel) Schematic presentation of the PRD1 life cycle. (A) The phage adsorbs onto the host surface. (B) The membrane transforms to the tubular form followed by DNA injection into the cytoplasm. (C and D) After DNA delivery, protein‐primed genome replication, transcription and translation take place. (E and F) During translation, the capsid proteins accumulate into the cytosol, whereas the viral membrane‐associated proteins are addressed to the cytoplasmic membrane. The cellular chaperone GroEL/GroES is necessary for the folding of several phage proteins. (G) Upon procapsid assembly, the virus‐specific patch is pinched off from the host cytoplasmic membrane and the soluble capsid proteins interact with the virus‐specific membrane. (H) The procapsid consisting of capsid enclosing the empty membrane is formed. (I) The genome is packaged into procapsid by the packaging ATPase P9 through a unique vertex. (J) The mature virions are released via lysis.
Figure 4. Cystovirus φ6. (a) A schematic presentation of the φ6 virion architecture and functions of the proteins. (b) Schematic presentation of the φ6 life cycle. (A) The phage adsorbs to the host pilus. (B) Fusion between viral envelope and host outer membrane. (C) Peptidoglycan digestion. (D and E) Penetration of plasma membrane. (F) Early transcription. (G and H) Assembly of empty polymerase complexes. (I) Sequential packaging of the three single‐stranded genomic precursor s, m and l into the empty polymerase complexes. (J and K) Synthesis of complementary RNA strands in the polymerase complex. (L) Late transcription. (M) Synthesis and assembly of nucleocapsid shell protein P8; synthesis of viral membrane proteins on the plasma membrane. (N) Intracellular translocation of envelopes onto the nucleocapsids; assembly of P3 spikes on the enveloped virions. (O) Release of mature virions by virus‐induced host cell lysis. Reproduced with permission from Poranen and Bamford (2011) © Springer.


Aalto AP, Bitto D, Ravantti JJ, et al. (2012) Snapshot of virus evolution in hypersaline environments from the characterization of a membrane‐containing Salisaeta icosahedral phage 1. Proceedings of the National Academy of Sciences, USA 109: 7079–7084.

Abrescia NG, Bamford DH, Grimes JM and Stuart DI (2012) Structure unifies the viral universe. Annual Review of Biochemistry 81: 795–822.

Abrescia NG, Cockburn JJ, Grimes JM, et al. (2004) Insights into assembly from structural analysis of bacteriophage PRD1. Nature 432: 68–74.

Abrescia NG, Grimes JM, Kivelä HM, et al. (2008) Insights into virus evolution and membrane biogenesis from the structure of the marine lipid‐containing bacteriophage PM2. Molecular Cell 31: 749–761.

Bamford DH (2003) Do viruses form lineages across different domains of life? Research in Microbiology 154: 231–236.

Bamford DH, Romantschuk M and Somerharju PJ (1987) Membrane fusion in prokaryotes: bacteriophage φ6 membrane fuses with the Pseudomonas syringae outer membrane. EMBO Journal 6: 1467–1473.

Bamford JK, Hänninen AL, Pakula TM, et al. (1991) Genome organization of membrane‐containing bacteriophage PRD1. Virology 183: 658–676.

Butcher SJ, Bamford DH and Fuller SD (1995) DNA packaging orders the membrane of bacteriophage PRD1. EMBO Journal 14: 6078–6086.

Butcher SJ, Grimes JM, Makeyev EV, Bamford DH and Stuart DI (2001) A mechanism for initiating RNA‐dependent RNA polymerization. Nature 410: 235–240.

Dahlberg JE and Franklin RM (1970) Structure and synthesis of a lipid‐containing bacteriophage. IV. Electron microscopic studies of PM2‐infected Pseudomonas BAL‐31. Virology 42: 1073–1086.

Dybvig K, Nowak JA, Sladek TL and Maniloff J (1985) Identification of an enveloped phage, mycoplasma virus L172, that contains a 14‐kilobase single‐stranded DNA genome. Journal of Virology 53: 384–390.

Espejo RT and Canelo ES (1968) Properties of bacteriophage PM2: a lipid‐containing bacterial virus. Virology 34: 738–747.

Frilander M and Bamford DH (1995) In vitro packaging of the single‐stranded RNA genomic precursors of the segmented double‐stranded RNA bacteriophage φ6: the three segments modulate each other's packaging efficiency. Journal of Molecular Biology 246: 418–428.

Gottlieb P, Metzger S, Romantschuk M, et al. (1988) Nucleotide sequence of the middle dsRNA segment of bacteriophage φ6: placement of the genes of membrane‐associated proteins. Virology 163: 183–190.

Gourlay RN (1971) Mycoplasmatales virus‐laidlawii 2, a new virus isolated from Acholeplasma laidlawii. Journal of General Virology 12: 65–67.

Grahn AM, Daugelavicius R and Bamford DH (2002) Sequential model of phage PRD1 DNA delivery: active involvement of the viral membrane. Molecular Microbiology 46: 1199–1209.

Hong C, Oksanen HM, Liu X, et al. (2014) A structural model of the genome packaging process in a membrane‐containing double stranded DNA virus. PLoS Biology 12: e1002024.

Huiskonen JT, de Haas F, Bubeck D, et al. (2006) Structure of the bacteriophage φ6 nucleocapsid suggests a mechanism for sequential RNA packaging. Structure 14: 1039–1048.

Jaatinen ST, Happonen LJ, Laurinmäki P, Butcher SJ and Bamford DH (2008) Biochemical and structural characterisation of membrane‐containing icosahedral dsDNA bacteriophages infecting thermophilic Thermus thermophilus. Virology 379: 10–19.

Kivelä HM, Daugelavicius R, Hankkio RH, Bamford JK and Bamford DH (2004) Penetration of membrane‐containing double‐stranded‐DNA bacteriophage PM2 into Pseudoalteromonas hosts. Journal of Bacteriology 186: 5342–5354.

Kivelä HM, Kalkkinen N and Bamford DH (2002) Bacteriophage PM2 has a protein capsid surrounding a spherical proteinaceous lipid core. Journal of Virology 76: 8169–8178.

Krupovic M and Bamford DH (2007) Putative prophages related to lytic tailless marine dsDNA phage PM2 are widespread in the genomes of aquatic bacteria. BMC Genomics 8: 236.

Krupovic M, Cvirkaite‐Krupovic V and Bamford DH (2008) Identification and functional analysis of the Rz/Rz1‐like accessory lysis genes in the membrane‐containing bacteriophage PRD1. Molecular Microbiology 68: 492–503.

Mancini EJ, Kainov DE, Grimes JM, et al. (2004) Atomic snapshots of an RNA packaging motor reveal conformational changes linking ATP hydrolysis to RNA translocation. Cell 118: 743–755.

Maniloff J, Kampo GJ and Dascher CC (1994) Sequence analysis of a unique temperature phage: mycoplasma virus L2. Gene 141: 1–8.

Männistö RH, Kivelä HM, Paulin L, Bamford DH and Bamford JK (1999) The complete genome sequence of PM2, the first lipid‐containing bacterial virus to be isolated. Virology 262: 355–363.

McGraw T, Mindich L and Frangione B (1986) Nucleotide sequence of the small double‐stranded RNA segment of bacteriophage φ6: novel mechanism of natural translational control. Journal of Virology 58: 142–151.

Mindich L, Bamford D, McGraw T and Mackenzie G (1982) Assembly of bacteriophage PRD1: particle formation with wild‐type and mutant viruses. Journal of Virology 44: 1021–1030.

Mindich L, Nemhauser I, Gottlieb P, et al. (1988) Nucleotide sequence of the large double‐stranded RNA segment of bacteriophage φ6: genes specifying the viral replicase and transcriptase. Journal of Virology 62: 1180–1185.

Mindich L, Qiao X, Qiao J, et al. (1999) Isolation of additional bacteriophages with genomes of segmented double‐stranded RNA. Journal of Bacteriology 181: 4505–4508.

Nemecek D, Qiao J, Mindich L, Steven AC and Heymann JB (2012) Packaging accessory protein P7 and polymerase P2 have mutually occluding binding sites inside the bacteriophage φ6 procapsid. Journal of Virology 86: 11616–11624.

Olkkonen VM, Ojala PM and Bamford DH (1991) Generation of infectious nucleocapsids by in vitro assembly of the shell protein on to the polymerase complex of the dsRNA bacteriophage φ6. Journal of Molecular Biology 218: 569–581.

Olsen RH, Siak JS and Gray RH (1974) Characteristics of PRD1, a plasmid‐dependent broad host range DNA bacteriophage. Journal of Virology 14: 689–699.

Peralta B, Gil‐Carton D, Castaño‐Díez D, et al. (2013) Mechanism of membranous tunnelling nanotube formation in viral genome delivery. PLoS Biology 11: e1001667.

Pirttimaa MJ and Bamford DH (2000) RNA secondary structures of the bacteriophage φ6 packaging regions. RNA 6: 880–889.

Poranen MM and Bamford DH (2011) Cystovirus, Cystoviridae. In: Tidona C and Darai G, (eds). The Springer Index of Viruses, 2nd edn. Dordrecht, The Netherlands: Springer.

Poranen MM, Daugelavicius R, Ojala PM, Hess MW and Bamford DH (1999) A novel virus‐host cell membrane interaction. Membrane voltage‐dependent endocytic‐like entry of bacteriophage φ6 nucleocapsid. Journal of Cell Biology 147: 671–682.

Poranen MM, Paatero AO, Tuma R and Bamford DH (2001) Self‐assembly of a viral molecular machine from purified protein and RNA constituents. Molecular Cell 7: 845–854.

Rissanen I, Grimes JM, Pawlowski A, et al. (2013) Bacteriophage P23‐77 capsid protein structures reveal the archetype of an ancient branch from a major virus lineage. Structure 21: 718–726.

Romantschuk M and Bamford DH (1985) Function of pili in bacteriophage φ6 penetration. Journal of General Virology 66: 2461–2469.

Rydman PS, Caldentey J, Butcher SJ, et al. (1999) Bacteriophage PRD1 contains a labile receptor‐binding structure at each vertex. Journal of Molecular Biology 291: 575–587.

Saren AM, Ravantti JJ, Benson SD, et al. (2005) A snapshot of viral evolution from genome analysis of the tectiviridae family. Journal of Molecular Biology 350: 427–440.

Savilahti H, Caldentey J, Lundström K, Syväoja JE and Bamford DH (1991) Overexpression, purification, and characterization of E. coli bacteriophage PRD1 DNA polymerase. In vitro synthesis of full‐length PRD1 DNA with purified proteins. Journal of Biological Chemistry 266: 18737–18744.

Uchiyama J, Takeuchi H, Kato S, et al. (2013) Characterization of Helicobacter pylori bacteriophage KHP30. Applied and Environmental Microbiology 79: 3176–3184.

van Dijk AA, Frilander M and Bamford DH (1995) Differentiation between minus‐ and plus‐strand synthesis: polymerase activity of dsRNA bacteriophage φ6 in an in vitro packaging and replication system. Virology 211: 320–323.

Vidaver AK, Koski RK and Van Etten JL (1973) Bacteriophage φ6: a lipid‐containing virus of Pseudomonas phaseolicola. Journal of Virology 11: 799–805.

Yu MX, Slater MR and Ackermann HW (2006) Isolation and characterization of Thermus bacteriophages. Archives of Virology 151: 663–679.

Further Reading

Abrescia NGA, Grimes JM, Fry EE, et al. (2010) What does it take to make a virus: the concept of the viral “self”. In: Stockley PG and Twarock R, (eds). Emerging Topics in Physical Virology, pp. 35–38. London: Imperial Collage Press.

Atanasova NS, Senčilo A, Pietilä MK, et al. (2015) Comparison of lipid‐containing bacterial and archaeal viruses. Advances in Virus Research, 92: 1–61.

Bamford JKH and Bamford DH (2006) Lipid‐containing bacteriophage PM2, the type organism of Corticoviridae. In: Calendar R, (ed). The Bacteriophages, pp. 171–174. New York: Oxford University Press.

Grahn AM, Butcher SJ, Bamford JKH and Bamford DH (2006) PRD1: dissecting the genome, structure, and entry. In: Calendar R, (ed). The Bacteriophages, pp. 161–170. New York: Oxford University Press.

Maniloff J (1992) Mycoplasma viruses. In: Maniloff J, McElhaney RN, Finch LR and Baseman JB, (eds). Mycoplasmas, Molecular Biology and Pathogenesis, pp. 41–59. Washington, DC: American Society for Microbiology.

Poranen MM, Tuma R and Bamford DH (2005) Assembly of double‐stranded RNA bacteriophages. Advances in Virus Research 64: 15–43.

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Poranen, Minna M, Bamford, Dennis H, and Oksanen, Hanna M(Apr 2015) Membrane‐Containing Bacteriophages. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000779.pub3]