Escherichia virus T4

2025-11-02T20:29:13Z

198.254.206.202: /* Adsorption and penetration */

{{Short description|Species of bacteriophage}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=April 2020}}
[[File:Bacteriophage T4 Structural Model at Atomic Resolution.tif|thumb|Bacteriophage T4 structure as per construction from individual PDBs and cryoEMs<ref>{{Cite journal|last=Padilla-Sanchez|first=Victor|date=2021|title=Structural Model of Bacteriophage T4|url=https://en.wikiversity.org/wiki/WikiJournal_of_Science/Structural_Model_of_Bacteriophage_T4|journal=WikiJournal of Science|volume=4|issue=1|pages=5|doi=10.15347/WJS/2021.005|doi-access=free}}</ref>]]
{{Virusbox
| name = Bacteriophage T4
| image = T4 phage EM.jpg
| image_caption = T4 phage ([[electron micrograph|EM]] of [[virion]])
| parent = Tequatrovirus
| species = Tequatrovirus T4
| synonyms =
* Enterobacteria phage T4
* Escherichia virus T4
| synonyms_ref = <ref>{{cite web |title=ICTV Taxonomy history: ''Escherichia virus T4'' |url=https://ictv.global/taxonomy/taxondetails?taxnode_id=20180332 |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=26 December 2018 |language=en |quote=''Caudovirales'' > ''Myoviridae'' > ''Tevenvirinae'' > ''T4virus'' > ''Escherichia virus T4''}}</ref>
| subdivision_ranks = Strains
| subdivision_ref = <ref name="ictv9">{{cite web |title=ICTV 9th Report (2011) ''Myoviridae'' |url=https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/68/myoviridae |archive-url=https://web.archive.org/web/20181226232821/https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/68/myoviridae |url-status=dead |archive-date=26 December 2018 |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=26 December 2018 |language=en }}</ref>
| subdivision =
* [[Enterobacteria phage C16]]
* [[Enterobacteria phage F10]]
* [[Enterobacteria phage Fs-alpha]]
* [[Enterobacteria phage PST]]
* [[Enterobacteria phage SKII]]
* [[Enterobacteria phage SKV]]
* [[Enterobacteria phage SKX]]
* [[Enterobacteria phage SV3]]
* [[Enterobacteria phage T2]]
* [[Enterobacteria phage T4]]
* [[Enterobacteria phage T6]]
}}

'''Escherichia virus T4''' is a species of [[bacteriophage]]s that infects ''[[Escherichia coli]]'' bacteria. It is a double-stranded DNA virus in the subfamily ''[[Tevenvirinae]]'' of the family ''[[Straboviridae]]''. T4 is capable of undergoing only a [[lytic|lytic life cycle]] and not the [[lysogeny|lysogenic life cycle]]. The species was formerly named '''T-even bacteriophage''', a name which also encompasses, among other strains (or isolates), [[Enterobacteria phage T2]], [[Enterobacteria phage T4]] and [[Enterobacteria phage T6]].

==Use in research==
Dating back to the 1940s and continuing today, T-even phages are considered the best studied model organisms. [[Model organisms]] are usually required to be simple with as few as five [[genes]]. Yet, T-even phages are in fact among the largest and highest complexity [[virus]], in which these phage's [[genetic information]] is made up of around 300 [[genes]]. Coincident with their complexity, T-even viruses were found to have the unusual base [[hydroxymethylcytosine]] (HMC) in place of the nucleic acid base [[cytosine]].<ref>{{Cite journal |last1=Wyatt |first1=G. R. |last2=Cohen |first2=S. S. |date=December 1952 |title=A New Pyrimidine Base from Bacteriophage Nucleic Acids |url=https://www.nature.com/articles/1701072a0 |journal=Nature |language=en |volume=170 |issue=4338 |pages=1072–1073 |doi=10.1038/1701072a0 |pmid=13013321 |bibcode=1952Natur.170.1072W |s2cid=4277592 |issn=1476-4687|url-access=subscription }}</ref>

==Genome and structure==
The T4 virus's double-stranded [[DNA]] [[genome]] is about 169 [[Base pair|kbp]] long<ref name="pmid12626685">{{cite journal | vauthors = Miller ES, Kutter E, Mosig G, Arisaka F, Kunisawa T, Rüger W | title = Bacteriophage T4 genome | journal = Microbiology and Molecular Biology Reviews | volume = 67 | issue = 1 | pages = 86–156, table of contents | date = March 2003 | pmid = 12626685 | pmc = 150520 | doi = 10.1128/mmbr.67.1.86-156.2003 }}</ref> and encodes 289 [[proteins]]. The T4 genome is [[Terminally redundant DNA|terminally redundant]]. Upon DNA replication, long multi-genome length concatemers are formed, perhaps by a rolling circle mechanism of replication.<ref name = Bernstein1973>{{cite journal | vauthors = Bernstein H, Bernstein C | title = Circular and branched circular concatenates as possible intermediates in bacteriophage T4 DNA replication | journal = Journal of Molecular Biology | volume = 77 | issue = 3 | pages = 355–61 | date = July 1973 | pmid = 4580243 | doi = 10.1016/0022-2836(73)90443-9 }}</ref> When packaged, the concatemer is cut at unspecific positions of the same length, leading to several genomes that represent [[circular permutation]]s of the original.<ref name="Brock">{{cite book | veditors = Madigan M, Martinko J | title = Brock Biology of Microorganisms | edition = 11th |publisher = Prentice Hall | year = 2006 | isbn = 978-0-13-144329-7 }}</ref> The T4 genome bears [[eukaryote]]-like [[intron]] sequences.

===Translation===
The [[Shine-Dalgarno sequence]] GAGG dominates in virus T4 early genes, whereas the sequence GGAG is a target for the T4 [[endonuclease]] RegB that initiates the early mRNA degradation.<ref name="pmid21533668">{{cite journal | vauthors = Malys N | title = Shine-Dalgarno sequence of bacteriophage T4: GAGG prevails in early genes | journal = Molecular Biology Reports | volume = 39 | issue = 1 | pages = 33–9 | date = January 2012 | pmid = 21533668 | doi = 10.1007/s11033-011-0707-4 | s2cid = 17854788 }}</ref>

==Virus particle structure==
[[Image:Tevenphage.svg|thumb|Structural overview of T2 phage]]
T4 is a relatively large virus, at approximately 90 [[nanometer|nm]] wide and 200 nm long (most viruses range from 25 to 200 nm in length). The DNA genome is held in an [[icosahedron|icosahedral]] head, also known as a [[capsid]].<ref>{{cite book|vauthors = Prescott LM, Harley JP, Klein DA|title=Microbiology|date=2008|publisher=McGraw-Hill|isbn=978-0-07-126727-4|edition=seventh}}</ref> The T4's tail is hollow so that it can pass its [[nucleic acid]] into the cell it is infecting after attachment. Myoviridae phages like T4 have complex contractile tail structures with a large number of proteins involved in the tail assembly and function.<ref name="pmid21129200">{{cite journal | vauthors = Leiman PG, Arisaka F, van Raaij MJ, Kostyuchenko VA, Aksyuk AA, Kanamaru S, Rossmann MG | title = Morphogenesis of the T4 tail and tail fibers | journal = Virology Journal | volume = 7 | pages = 355 | date = December 2010 | pmid = 21129200 | pmc = 3004832 | doi = 10.1186/1743-422X-7-355 | doi-access = free }}</ref> The tail fibres are also important in recognizing host cell surface receptors, so they determine if a bacterium is within the virus's host range.<ref name="pmid9672598">{{cite journal | vauthors = Ackermann HW, Krisch HM | title = A catalogue of T4-type bacteriophages | journal = Archives of Virology | volume = 142 | issue = 12 | pages = 2329–45 | date = 1997 | pmid = 9672598 | doi = 10.1007/s007050050246 | s2cid = 39369249 }}</ref>

The structure of the 6 megadalton T4 baseplate that comprises 127 polypeptide chains of 13 different proteins (gene products 5, 5.4, 6, 7, 8, 9, 10, 11, 12, 25, 27, 48 and 53) has recently been described in atomic detail. An atomic model of the proximal region of the tail tube formed by gp54 and the main tube protein gp19 have also been created. The tape measure protein gp29 is present in the baseplate-tail tube complexes, but it could not be modeled.<ref name="pmid27193680">{{cite journal | vauthors = Taylor NM, Prokhorov NS, Guerrero-Ferreira RC, Shneider MM, Browning C, Goldie KN, Stahlberg H, Leiman PG | title = Structure of the T4 baseplate and its function in triggering sheath contraction | journal = Nature | volume = 533 | issue = 7603 | pages = 346–52 | date = May 2016 | pmid = 27193680 | doi = 10.1038/nature17971 | bibcode = 2016Natur.533..346T | s2cid = 4399265 }}</ref>

During assembly of the bacteriophage (phage) T4 [[virus|virion]], the morphogenetic proteins encoded by the phage [[gene]]s interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 morphogenesis.<ref name="pmid4907266">{{cite journal | vauthors = Floor E | title = Interaction of morphogenetic genes of bacteriophage T4 | journal = Journal of Molecular Biology | volume = 47 | issue = 3 | pages = 293–306 | date = February 1970 | pmid = 4907266 | doi = 10.1016/0022-2836(70)90303-7}}</ref> Phage T4 encoded proteins that determine virion structure include major structural components, minor structural components and non-structural proteins that catalyze specific steps in the morphogenesis sequence.<ref name="pmid4878023">{{cite journal | vauthors = Snustad DP | title = Dominance interactions in Escherichia coli cells mixedly infected with bacteriophage T4D wild-type and amber mutants and their possible implications as to type of gene-product function: catalytic vs. stoichiometric | journal = Virology | volume = 35 | issue = 4 | pages = 550–63 | date = August 1968 | pmid = 4878023 | doi = 10.1016/0042-6822(68)90285-7 }}</ref> Phage T4 morphogenesis is divided into three independent pathways: the head, the tail and the long tail fibres as detailed by Yap and Rossman.<ref name="pmid25517898">{{cite journal | vauthors = Yap ML, Rossmann MG | title = Structure and function of bacteriophage T4 | journal = Future Microbiology | volume = 9 | issue = 12 | pages = 1319–27 | date = 2014 | pmid = 25517898 | pmc = 4275845 | doi = 10.2217/fmb.14.91}}</ref>

==Infection process==
The T4 virus initiates an ''Escherichia coli'' [[infection]] by binding OmpC [[porin (protein)|porin]] proteins and [[lipopolysaccharide]] (LPS) on the surface of ''E. coli'' cells with its long tail fibers (LTF).<ref name="Yu1982">{{cite journal | vauthors = Yu F, Mizushima S | title = Roles of lipopolysaccharide and outer membrane protein OmpC of Escherichia coli K-12 in the receptor function for bacteriophage T4 | journal = Journal of Bacteriology | volume = 151 | issue = 2 | pages = 718–22 | date = August 1982 | pmid = 7047495 | pmc = 220313 | doi = 10.1128/JB.151.2.718-722.1982 }}</ref><ref name="Furukawa1982">{{cite journal | vauthors = Furukawa H, Mizushima S | title = Roles of cell surface components of Escherichia coli K-12 in bacteriophage T4 infection: interaction of tail core with phospholipids | journal = Journal of Bacteriology | volume = 150 | issue = 2 | pages = 916–24 | date = May 1982 | pmid = 7040345 | pmc = 216445 | doi = 10.1128/JB.150.2.916-924.1982 }}</ref> A recognition signal is sent through the LTFs to the baseplate. This unravels the short tail fibers (STF) that bind irreversibly to the ''E. coli'' cell surface. The baseplate changes conformation and the tail sheath contracts, causing GP5 at the end of the tail tube to puncture the outer [[cell membrane|membrane]] of the cell.<ref name="Maghsoodi Chatterjee Andricioaei Perkins pp. 25097–25105">{{cite journal | vauthors = Maghsoodi A, Chatterjee A, Andricioaei I, Perkins NC | title = How the phage T4 injection machinery works including energetics, forces, and dynamic pathway | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 50 | pages = 25097–25105 | date = December 2019 | pmid = 31767752 | pmc = 6911207 | doi = 10.1073/pnas.1909298116 | bibcode = 2019PNAS..11625097M |doi-access=free }}</ref> The [[lysozyme]] domain of GP5 is activated and degrades the periplasmic [[peptidoglycan]] layer. The remaining part of the membrane is degraded and then DNA from the head of the virus can travel through the tail tube and enter the ''E. coli'' cell.{{citation needed|date=October 2022}}

In 1952, Hershey and Chase<ref name = Hershey1952>{{cite journal | vauthors = HERSHEY AD, CHASE M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | journal = The Journal of General Physiology | volume = 36 | issue = 1 | pages = 39–56 | date = May 1952 | pmid = 12981234 | pmc = 2147348 | doi = 10.1085/jgp.36.1.39 }}</ref> provided key evidence that the phage DNA, as distinct from protein, enters the host bacterial cell upon infection and is thus the genetic material of the phage. This finding suggested that DNA is, in general, the genetic material of different organisms.{{citation needed|date=October 2022}}

===Reproduction===
The [[lytic cycle|lytic life cycle]] (from entering a bacterium to its destruction) takes approximately 30 minutes (at 37 °C). Virulent bacteriophages multiply in their bacterial host immediately after entry. After the number of progeny phages reach a certain amount, they cause the host to lyse or break down, therefore they would be released and infect new host cells.<ref>{{cite book|last1=Sherwood|first1=Linda|title=Prescott's Microbiology|date=2011|publisher=McGraw-Hill|edition=eighth}}</ref> The process of host lyses and release is called the [[lytic cycle]]. Lytic cycle is a cycle of viral reproduction that involves the destruction of the infected cell and its membrane. This cycle involves a virus that overtakes the host cell and its machinery to reproduce. Therefore, the virus must go through 5 stages in order to reproduce and infect the host cell:{{citation needed|date=October 2022}}
* [[Adsorption]] and penetration (starting immediately)
* Arrest of host [[gene expression]] (starting immediately)
* [[Enzyme]] synthesis (starting after 5 minutes)
* [[DNA replication]] (starting after 10 minutes)
* Formation of new [[virus]] particles (starting after 12 minutes)
After the life cycle is complete, the host cell [[lysis|bursts open]] and ejects the newly built viruses into the environment, destroying the host cell. T4 has a burst size of approximately 100–150 viral particles per infected host.{{citation needed|date=October 2022}}

Benzer (1955 – 1959) developed a system for studying the fine structure of the gene using bacteriophage T4 mutants defective in the ''rIIA'' and ''rIIB'' genes.<ref>Benzer S. "Adventures in the rII region" in Phage and the Origins of Molecular Biology (2007) Edited by John Cairns, Gunther S. Stent, and James D. Watson, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, Long Island, New York {{ISBN|978-0879698003}}</ref><ref name="pmid16589677">{{cite journal | vauthors = Benzer S | title = Fine structure of a genetic region in bacteriophage| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 41 | issue = 6 | pages = 344–54 | date = June 1955 | pmid = 16589677 | pmc = 528093 | doi = 10.1073/pnas.41.6.344 | bibcode = 1955PNAS...41..344B| doi-access = free}}</ref><ref name="pmid16590553">{{cite journal | vauthors = Benzer S | title = On the topology of genetic fine structure| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 45 | issue = 11 | pages = 1607–20 | date = November 1959 | pmid = 16590553 | pmc = 222769 | doi = 10.1073/pnas.45.11.1607 | bibcode = 1959PNAS...45.1607B| doi-access = free}}</ref> The techniques employed were [[complementation (genetics)|complementation]] tests and crosses to detect [[genetic recombination|recombination]], particularly between deletion mutations. These genetic experiments led to the finding of a unique linear order of mutational sites within the genes. This result provided strong evidence for the key idea that the gene has a linear structure equivalent to a length of DNA with many sites that can independently mutate.{{citation needed|date=October 2022}}

====Adsorption and penetration====
[[File:Phage injection.png|thumb|right|Diagram of the DNA injection process]]
Just like all other viruses, even phages do not randomly attach to the surface of their host; instead, they "search" and bind to [[Cell surface receptor|receptor]]s, specific [[protein]] structures, found on the surface of the host. These receptors vary with the phage; [[teichoic acid]], cell wall proteins and [[lipopolysaccharides]], [[flagella]], and [[pilus|pili]] all can serve as receptors for the phage to bind to. For the T-even phage to infect its host and begin its life cycle, it must enter the first process of [[infection]], [[adsorption]] of the phage to the bacterial cell. Adsorption is a value characteristic of the phage-host pair, and the adsorption of the phage on the host cell surface is illustrated as a 2-stage process: reversible and irreversible. It involves the phage's tail structure that begins when the phage's tail fibres help bind the phage to the appropriate receptor of its host. This process is reversible. One or more of the components of the base plate mediates the reversible process of binding of the phage to a bacterium.{{citation needed|date=October 2022}}

Penetration is also a value characteristic of phage-host [[infection]] that involves the injection of the phages [[genetic material]] inside the [[Bacteria|bacterium]]. Penetration of [[nucleic acid]] takes place after the irreversible adsorption phase. Mechanisms involving penetration of the phage's nucleic acid are specific for each phage. This penetration mechanism can involve [[Electrical excitability|electrochemical membrane potential]], [[Adenosine triphosphate|ATP]] molecules, enzymatic splitting of [[peptidoglycan]] layer, or all three of these factors can be vital for the penetration of the nucleic acid inside the bacterial cell. Studies have been done on the [[T4-like viruses|T2 bacteriophage]] (T4-like phage) mechanism of penetration, and it has been shown that the phage's tail does not penetrate inside the bacterial cell wall, and penetration of this phage involves electrochemical [[membrane potential]] on the inner membrane.<ref>{{cite book|last1=Norkin|first1=Leonard C.|title=Virology, Molecular Biology and Pathogenesis|date=2010|publisher=American Society for Microbiology|location=Washington|isbn=978-1-55581-453-3|page=31}}</ref><ref>{{cite book|vauthors = Prescott LM, Harley JP, Klein DA|title=Microbiology|date=2008|publisher=McGraw Hill|isbn=978-0-07-126727-4|page=427|edition=seventh}}</ref>

==Replication and packaging==
Virus T4 genome is synthesized within the host cell using rolling circle replication.<ref name = Bernstein1973/> The time it takes for DNA replication in a living cell was measured as the rate of virus T4 DNA elongation in virus-infected E. coli.<ref>{{cite journal | vauthors = McCarthy D, Minner C, Bernstein H, Bernstein C | year = 1976 | title = DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant | journal = J Mol Biol | volume = 106 | issue = 4| pages = 963–81 | pmid = 789903 | doi=10.1016/0022-2836(76)90346-6}}</ref> During the period of exponential DNA increase at 37 °C, the rate was 749 nucleotides per second. The mutation rate per base pair per replication during virus T4 DNA synthesis is 1.7 per 10<sup>−8</sup>,<ref>Drake JW (1970) ''The Molecular Basis of Mutation.'' Holden-Day, San Francisco {{ISBN|0816224501}} {{ISBN|978-0816224500}}</ref> a highly accurate DNA copying mechanism, with only 1 error in 300 copies. The virus also codes for unique [[DNA repair]] mechanisms.<ref name = Bernstein1981>{{cite journal | vauthors = Bernstein C | year = 1981 | title = Deoxyribonucleic acid repair in bacteriophage | journal = Microbiol. Rev. | volume = 45 | issue = 1| pages = 72–98 | pmid = 6261109 | pmc = 281499 }}</ref> The T4 phage head is assembled empty around a scaffolding protein, which is later degraded. Consequently, the DNA needs to enter the prohead through a tiny pore, which is achieved by a hexamer of gp17 interacting with DNA first, which also serves as a motor and nuclease. The T4 DNA packaging motor has been found to load DNA into virus capsids at a rate up to 2000 base pairs per second. The power involved, if scaled up in size, would be equivalent to that of an average automobile engine.<ref name="pmid21129201">{{cite journal | vauthors = Rao VB, Black LW | title = Structure and assembly of bacteriophage T4 head | journal = Virology Journal | volume = 7 | pages = 356 | date = December 2010 | pmid = 21129201 | pmc = 3012670 | doi = 10.1186/1743-422X-7-356 | doi-access = free }}</ref>

==Release==
The final step in viral reproduction and multiplication is determined by the release of virions from the host cell. The release of the virions occurs after the breakage of the bacterial plasma membrane. Nonenveloped viruses lyse the host cell which is characterized by viral proteins attacking the peptidoglycan or membrane. The lysis of the bacteria occurs when the capsids inside the cell release the enzyme lysozyme which break down the cell wall. The released bacteriophages infect other cells, and the viral multiplication cycle is repeated within those cells.{{citation needed|date=October 2022}}

==Multiplicity reactivation==
[[File:Phage T4 multiplicity reactivation.jpg|thumb|Survival curves for virus T4 with DNA damaged by UV (top) or MMC (bottom) after single virus T4 infecting host cells (monocomplexes) or two or more virus T4 simultaneously infecting host cells (multicomplexes).]]

Multiplicity reactivation (MR) is the process by which two or more virus genomes, each containing inactivating genome damage, can interact within an infected cell to form a viable virus genome. [[Salvador Luria]], while studying UV irradiated virus T4 in 1946, discovered MR and proposed that the observed reactivation of damaged virus occurs by a recombination mechanism.(see refs.<ref name="pmid16588748">{{cite journal |vauthors=Luria SE |title=Reactivation of Irradiated Bacteriophage by Transfer of Self-Reproducing Units |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=33 |issue=9 |pages=253–64 |year=1947 |pmid=16588748 |pmc=1079044 |doi= 10.1073/pnas.33.9.253|bibcode=1947PNAS...33..253L |doi-access=free }}</ref><ref name="pmid18100306">{{cite journal |vauthors=LURIA SE, DULBECCO R |title=Lethal mutations, and inactivation of individual genetic determinants in bacteriophage |journal=Genetics |volume=33 |issue=6 |pages=618 |year=1948 |pmid=18100306 }}</ref><ref name="pmid17247312">{{cite journal |vauthors=Luria SE, Dulbecco R |title=Genetic Recombinations Leading to Production of Active Bacteriophage from Ultraviolet Inactivated Bacteriophage Particles |journal=Genetics |volume=34 |issue=2 |pages=93–125 |year=1949 |doi=10.1093/genetics/34.2.93 |pmid=17247312 |pmc=1209443 }}</ref>) This preceded the confirmation of DNA as the genetic material in 1952 in related virus T2 by the [[Hershey–Chase experiment]].<ref name = Hershey1952/>

As remembered by Luria (1984,<ref name = Luria1984>Salvador E. Luria. A Slot Machine, A Broken Test Tube: An Autobiography. Harper & Row, New York: 1984. Pp. 228. {{ISBN|0-06-015260-5}} (USA and Canada)</ref> pg. 97) the discovery of reactivation of irradiated virus (referred to as "[[multiplicity reactivation]]") immediately started a flurry of activity in the study of repair of radiation damage within the early [[phage group]] (reviewed by Bernstein<ref name = Bernstein1981/> in 1981). It turned out later that the repair of damaged virus by mutual help that Luria had discovered was only one special case of DNA repair. Cells of all types, not just, bacteria and their viruses, but all organisms studied, including humans, are now known to have complex biochemical processes for repairing DNA damages (see [[DNA repair]]). DNA repair processes are also now recognized as playing critical roles in protecting against [[DNA repair#DNA repair and aging|aging]], [[Carcinogenesis#DNA damage and deficient DNA repair in carcinogenesis|cancer]], and [[Infertility#Other causes|infertility]].{{citation needed|date=October 2022}}

MR is usually represented by "survival curves" where survival of plaque forming ability of multiply infected cells (multicomplexes) is plotted against dose of genome damaging agent. For comparison, the survival of virus plaque forming ability of singly infected cells (monocomplexes) is also plotted against dose of genome damaging agent. The top figure shows the survival curves for virus T4 multicomplexes and monocomplexes with increasing dose of UV light. Since survival is plotted on a log scale it is clear that survival of multicomplexes exceeds that of monocomplexes by very large factors (depending on dose). The UV inactivation curve for multicomplexes has an initial shoulder. Other virus T4 DNA damaging agents with shoulders in their multicomplex survival curves are X-rays<ref name="pmid14938320">{{cite journal |vauthors=WATSON JD |title=The properties of x-ray inactivated bacteriophage |journal=J. Bacteriol. |volume=63 |issue=4 |pages=473–85 |year=1952 |pmid=14938320 |pmc=169298 |doi= 10.1128/JB.63.4.473-485.1952}}</ref><ref name="pmid13544109">{{cite journal |vauthors=HARM W |title=Multiplicity reactivation, marker rescue, and genetic recombination in phage T4 following x-ray inactivation |journal=Virology |volume=5 |issue=2 |pages=337–61 |year=1958 |pmid=13544109 |doi= 10.1016/0042-6822(58)90027-8}}</ref> and ethyl methane sulfonate (EMS).<ref name = Bernstein1981/> The presence of a shoulder has been interpreted to mean that two recombinational processes are used.<ref name=Yarosh>{{cite journal |vauthors=Yarosh DB |title=UV-induced mutation in bacteriophage T4 |journal=J. Virol. |volume=26 |issue=2 |pages=265–71 |year=1978 |pmid=660716 |pmc=354064 |doi= 10.1128/JVI.26.2.265-271.1978}}</ref> The first one repairs DNA with high efficiency (in the "shoulder"), but is saturated in its ability as damage increases; the second pathway functions at all levels of damage. Surviving T4 virus released from multicomplexes show no increase in [[mutation]], indicating that MR of UV irradiated virus is an accurate process.<ref name=Yarosh />

The bottom figure shows the survival curves for inactivation of virus T4 by the DNA damaging agent [[Mitomycins|mitomycin C]] (MMC). In this case the survival curve for multicomplexes has no initial shoulder, suggesting that only the second recombinational repair process described above is active. The efficiency of repair by this process is indicated by the observation that a dose of MMC that allows survival of only 1 in 1,000 monocomplexes allows survival of about 70% of multicomplexes. Similar multicomplex survival curves (without shoulders) were also obtained for the DNA damaging agents [[Phosphorus#Isotopes|P32]] decay, [[Psoralen#Repair of psoralen DNA adducts|psoralen]] plus near-UV irradiation (PUVA), [[Methylnitronitrosoguanidine|N-methyl-N'-nitro-N-nitrosoguanidine]] (MNNG), [[Methyl methanesulfonate|methyl methane sulfonate]] (MMS) and [[nitrous acid]].<ref name = Bernstein1981/>

Several of the genes found to be necessary for MR in virus T4 proved to be [[Homology (biology)#Orthology|orthologs]] for genes essential for recombination in [[prokaryote]]s, [[eukaryote]]s and [[archaea]]. This includes, for instance, T4 gene ''uvsX''<ref name="pmid8456313">{{cite journal |vauthors=Story RM, Bishop DK, Kleckner N, Steitz TA |title=Structural relationship of bacterial RecA proteins to recombination proteins from bacteriophage T4 and yeast |journal=Science |volume=259 |issue=5103 |pages=1892–6 |year=1993 |pmid=8456313 |doi= 10.1126/science.8456313|bibcode=1993Sci...259.1892S }}</ref> which specifies a protein that has three-dimensional structural homology to [[RecA]] from ''[[Escherichia coli]]'' and the homologous protein [[RAD51]] in [[eukaryotes]] and RadA in [[archaea]]. It has been suggested that the efficient and accurate recombinational repair of DNA damages during MR may be analogous to the recombinational repair process that occurs during [[meiosis]] in [[eukaryotes]].<ref name="pmid573881">{{cite journal |vauthors=Bernstein C |title=Why are babies young? Meiosis may prevent aging of the germ line |journal=Perspect. Biol. Med. |volume=22 |issue=4 |pages=539–44 |year=1979 |pmid=573881 |doi= 10.1353/pbm.1979.0041|s2cid=38550472 }}</ref>

==History==
Bacteriophages were first discovered by the English scientist [[Frederick Twort]] in 1915 and [[Félix d'Hérelle]] in 1917. In the late 1930s, T. L. Rakieten proposed either a mixture of raw sewerage or a lysate from ''E. coli'' infected with raw sewerage to the two researchers [[Milislav Demerec]] and [[Ugo Fano]]. These two researchers isolated T3, T4, T5, and T6 from ''E.coli''. Also, in 1932, the researcher J. Bronfenbrenner had studied and worked on the T2 phage, at which the T2 phage was isolated from the virus.<ref>{{cite book|last1=Willey|first1=Joanne|title=Prescott's Microbiology|publisher=McGraw-Hill|edition=seventh}}</ref> This isolation was made from a fecal material rather than from sewerage. At any rate, [[Max Delbrück]] was involved in the discovery of the T even phages. His part was naming the bacteriophages into Type 1(T1), Type 2 (T2), Type 3 (T3), etc.{{citation needed|date=October 2022}}

The specific time and place of T4 virus isolation remains unclear, though they were likely found in sewage or fecal material. T4 and similar viruses were described in a paper by [[Thomas F. Anderson]], Max Delbrück, and Milislav Demerec in November 1944.<ref name="pmid10835374">{{cite journal | vauthors = Abedon ST | title = The murky origin of Snow White and her T-even dwarfs | journal = Genetics | volume = 155 | issue = 2 | pages = 481–6 | date = June 2000 | doi = 10.1093/genetics/155.2.481 | pmid = 10835374 | pmc = 1461100}}</ref>
In 1943, [[Salvador Luria]] and Delbrück showed that bacterial [[mutations]] for phage resistance arise in the absence of [[Selection (biology)|selection]], rather than being a response to selection.<ref name = Luria1984/> The traditional wisdom among bacteriologists prior to 1943 was that bacteria had no chromosomes and no genes. The Luria–Delbrück experiment showed that bacteria, like other established model genetic organisms, have genes, and that these can spontaneously mutate to generate mutants that may then reproduce to form clonal lineages. That year, they also began working with [[Alfred Hershey]], another phage experimenter.<ref>Morange, ''A History of Molecular Biology'', pp 43-44</ref> (The three would share the 1969 [[Nobel Prize in Physiology or Medicine]], "for work on the replication mechanism and genetics of viruses".)

The [[phage group]] was an informal network of biologists centered on Max Delbrück that carried out basic research mainly on bacteriophage T4 and made numerous seminal contributions to [[microbial genetics]] and the [[history of molecular biology|origins of molecular biology]] in the mid-20th century. In 1961, [[Sydney Brenner]], an early member of the phage group, collaborated with [[Francis Crick]], [[Leslie Barnett]] and Richard Watts-Tobin at the Cavendish Laboratory in Cambridge to perform genetic experiments that demonstrated the basic nature of the [[genetic code]] for proteins.<ref name="pmid13882203">{{cite journal | vauthors = CRICK FH, BARNETT L, BRENNER S, WATTS-TOBIN RJ | title = General nature of the genetic code for proteins | journal = Nature | volume = 192 | pages = 1227–32 | date = December 1961 | issue = 4809 | pmid = 13882203 | doi = 10.1038/1921227a0 | bibcode = 1961Natur.192.1227C | s2cid = 4276146 }}</ref> These experiments, carried out with mutants of the rIIB gene of phage T4, showed, that for a gene that encodes a protein, three sequential bases of the gene's DNA specify each successive amino acid of the protein. Thus the genetic code is a triplet code, where each triplet (called a codon) specifies a particular amino acid. They also obtained evidence that the codons do not overlap with each other in the DNA sequence encoding a protein, and that such a sequence is read from a fixed starting point.{{citation needed|date=October 2022}}

During 1962–1964 phage T4 researchers provided an opportunity to study the function of virtually all of the genes that are essential for growth of the phage under laboratory conditions.<ref>Edgar RS Conditional lethals: in Phage and the Origins of Molecular Biology (2007) Edited by John Cairns, Gunther S. Stent, and James D. Watson, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, Long Island, New York {{ISBN|978-0879698003}}</ref><ref name="pmid15514035">{{cite journal | vauthors = Edgar B | title = The genome of bacteriophage T4: an archeological dig | journal = Genetics | volume = 168 | issue = 2 | pages = 575–82 | date = October 2004 | doi = 10.1093/genetics/168.2.575 | pmid = 15514035 | pmc = 1448817 }}</ref> These studies were facilitated by the discovery of two classes of [[lethal allele|conditional lethal mutants]]. One class of such mutants is known as [[stop codon|amber mutants]].<ref name="EpsteinBolle1963">{{cite journal|vauthors = Epstein RH, Bolle A, Steinberg CM, Kellenberger E, Boy de la Tour E, Chevalley R, Edgar RS, Susman M, Denhardt GH, Lielausis A|title = Physiological Studies of Conditional Lethal Mutants of Bacteriophage T4D|journal = Cold Spring Harbor Symposia on Quantitative Biology|volume = 28|year = 1963|pages = 375–394|issn = 0091-7451|doi = 10.1101/SQB.1963.028.01.053}}</ref> Another class of conditional lethal mutants is referred to as [[temperature-sensitive mutant]]s<ref name="pmid14156925">{{cite journal | vauthors = Edgar RS, Lielausis I | title = Temperature-sensitive mutants of bacteriophage T4D: Their isolation and Characterization.| journal = Genetics | volume = 49 | pages = 649–62 | date = April 1964 | issue = 4| doi = 10.1093/genetics/49.4.649| pmid = 14156925 | pmc = 1210603}}</ref> Studies of these two classes of mutants led to considerable insight into numerous fundamental biologic problems. Thus understanding was gained on the functions and interactions of the proteins employed in the machinery of [[DNA replication]], [[DNA repair|repair]] and [[genetic recombination|recombination]], and on how viruses are assembled from protein and nucleic acid components (molecular [[morphogenesis]]). Furthermore, the role of [[stop codon|chain terminating codons]] was elucidated. One noteworthy study used amber mutants defective in the gene encoding the major head protein of phage T4.<ref name="pmid14085558">{{cite journal | vauthors = Sarabhai AS, Stretton AO, Brenner S, Bolle A| title = Co-linearity of the gene with the polypeptide chain| journal = Nature | volume = 201 | pages = 13–7 | date = January 1964 | issue = 4914| pmid = 14085558 | doi = 10.1038/201013a0 | bibcode = 1964Natur.201...13S| s2cid = 10179456}}</ref> This experiment provided strong evidence for the widely held, but prior to 1964 still unproven, "sequence hypothesis" that the [[protein primary structure|amino acid sequence]] of a protein is specified by the [[nucleic acid sequence|nucleotide sequence]] of the [[gene]] determining the protein. Thus, this study demonstrated the co-linearity of the gene with its encoded protein.

A number of [[Nobel Prize]] winners worked with virus T4 or T4-like viruses including [[Max Delbrück]], [[Salvador Luria]], [[Alfred Hershey]], [[James D. Watson]], and [[Francis Crick]]. Other important scientists who worked with virus T4 include [[Michael Rossmann]], [[Seymour Benzer]], [[Bruce Alberts]], [[Gisela Mosig]],<ref name="pmid15579671">{{cite journal | vauthors = Nossal NG, Franklin JL, Kutter E, Drake JW | title = Anecdotal, historical and critical commentaries on genetics. Gisela Mosig | journal = Genetics | volume = 168 | issue = 3 | pages = 1097–104 | date = November 2004 | doi = 10.1093/genetics/168.3.1097 | pmid = 15579671 | pmc = 1448779}}</ref> [[Richard Lenski]], and [[James J. Bull|James Bull]].

==See also==
{{Portal|Viruses}}
* [[T4 rII system|T4 ''rII'' system]]
* [[T2 phage]]
* [[Enterobacteria phage T6|T6 phage]]
* [[Bacteriophage]]
* [[Virology]]

==References==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | doi=10.1007/s00018-003-3072-1 | pmid=14625682 | author=Leiman P.G. | author2=Kanamaru S | author3=Mesyanzhinov V.V. | author4=Arisaka F. | author5=Rossmann M.G. | title=Structure and morphogenesis of bacteriophage T4. | journal= Cellular and Molecular Life Sciences | volume=60 | number=11 | pages=2356–2370 | year=2003| s2cid=2228357 | pmc=11138918 }}
* Karam, J., Petrov, V., Nolan, J., Chin, D., Shatley, C., Krisch, H., and Letarov, A. The T4-like phages genome project. [https://web.archive.org/web/20070523215704/http://phage.bioc.tulane.edu/ https://web.archive.org/web/20070523215704/http://phage.bioc.tulane.edu/]. '' (The T4-like phage full genomic sequence depository)''
* Mosig, G., and F. Eiserling. 2006. T4 and related phages: structure and development, R. Calendar and S. T. Abedon (eds.), The Bacteriophages. Oxford University Press, Oxford. ''(Review of phage T4 biology)'' {{ISBN|0-19-514850-9}}
* {{cite journal |doi=10.1073/pnas.0503404102 |author=Filee J. Tetart F. |author2=Suttle C.A. |author3=Krisch H.M. |title=Marine T4-type bacteriophages, a ubiquitous component of the dark matter of the biosphere |journal=Proc. Natl. Acad. Sci. USA |volume=102 |issue=35 |pages=12471–6 |year=2005 |pmid=16116082 |pmc=1194919|bibcode=2005PNAS..10212471F |doi-access=free }} ''(Indication of prevalence and T4-like phages in the wild)''
* {{cite journal |doi=10.1128/JB.186.24.8276-8286.2004 |author=Chibani-Chennoufi S. |author2=Canchaya C. |author3=Bruttin A. |author4=Brussow H. |title=Comparative genomics of the T4-Like ''Escherichia coli'' phage JS98: implications for the evolution of T4 phages |journal=J. Bacteriol. |volume=186 |issue=24 |pages=8276–86 |year=2004 |pmid=15576776 |pmc=532421}} ''(Characterization of a T4-like phage)''
* {{cite journal |vauthors=Desplats C, Krisch HM |title=The diversity and evolution of the T4-type bacteriophages |journal=Res. Microbiol. |volume=154 |issue=4 |pages=259–67 |date=May 2003 |pmid=12798230 |doi=10.1016/S0923-2508(03)00069-X |doi-access=free }}
* {{cite journal |doi=10.1128/MMBR.67.1.86-156.2003 |author=Miller, E.S. |author2=Kutter E. |author3=Mosig G. |author4=Arisaka F. |author5=Kunisawa T. |author6=Ruger W. |title=Bacteriophage T4 genome |journal=Microbiol. Mol. Biol. Rev. |volume=67 |issue=1 |pages=86–156 |year=2003 |pmid=12626685 |pmc=150520}} ''(Review of phage T4, from the perspective of its genome)''
* {{cite journal |doi=10.1128/JB.184.10.2789-2804.2002 |author=Desplats C. |author2= Dez C. |author3=Tetart F. |author4=Eleaume H. |author5=Krisch H.M. |title=Snapshot of the genome of the pseudo-T-even bacteriophage RB49 |journal=J. Bacteriol. |volume=184 |issue=10 |pages=2789–2804 |year=2002 |pmid=11976309 |pmc=135041}} ''(Overview of the RB49 genome, a T4-like phage)''
* {{cite journal | vauthors=Malys N, Chang DY, Baumann RG, Xie D, Black LW | title = A bipartite bacteriophage T4 SOC and HOC randomized peptide display library: detection and analysis of phage T4 terminase (gp17) and late sigma factor (gp55) interaction |journal = J Mol Biol |volume = 319 | issue = 2 | pages = 289–304 | year = 2002 | pmid = 12051907 | doi =10.1016/S0022-2836(02)00298-X }} ''(T4 phage application in biotechnology for studying protein interaction)''
* {{cite journal |doi=10.1128/JB.183.1.358-366.2001 |author=Tétart F. |author2=Desplats C. |author3=Kutateladze M. |author4=Monod C. |author5=Ackermann H.-W. |author6=Krisch H.M. |title=Phylogeny of the major head and tail genes of the wide-ranging T4-type bacteriophages |journal=J. Bacteriol. |volume=183 |issue=1 |pages=358–366 |year=2001 |pmid=11114936 |pmc=94885}} ''(Indication of the prevalence of T4-type sequences in the wild)''
* {{cite journal |author=Abedon S.T. |title=The murky origin of Snow White and her T-even dwarfs |journal=Genetics |volume=155 |issue=2 |pages=481–6 |year=2000 |doi=10.1093/genetics/155.2.481 |url=http://www.genetics.org/cgi/content/full/155/2/481 |pmid=10835374 |pmc=1461100}} ''(Historical description of the isolation of the T4-like phages T2, T4, and T6)''
* {{cite journal |doi=10.1007/s007050050246 |vauthors=Ackermann HW, Krisch HM |title=A catalogue of T4-type bacteriophages |journal=Arch. Virol. |volume=142 |issue=12 |pages=2329–45 |year=1997 |pmid=9672598 |s2cid=39369249 |url=http://link.springer.de/link/service/journals/00705/bibs/7142012/71422329.htm |url-status=dead |archive-url=https://web.archive.org/web/20011101134153/http://link.springer.de/link/service/journals/00705/bibs/7142012/71422329.htm |archive-date=1 November 2001 |url-access=subscription }} ''(Nearly complete list of then-known T4-like phages)''
* {{cite journal |vauthors=Monod C, Repoila F, Kutateladze M, Tétart F, Krisch HM |title=The genome of the pseudo T-even bacteriophages, a diverse group that resembles T4 |journal=J. Mol. Biol. |volume=267 |issue=2 |pages=237–49 |date=March 1997 |pmid=9096222 |doi=10.1006/jmbi.1996.0867 }} ''(Overview of various T4-like phages from the perspective of their genomes)''
* {{cite journal |doi=10.1007/BF01728666 |author=Kutter E. |author2=Gachechiladze K. |author3=Poglazov A. |author4=Marusich E. |author5=Shneider M. |author6=Aronsson P. |author7=Napuli A. |author8=Porter D. |author9=Mesyanzhinov V. |title=Evolution of T4-related phages |journal=Virus Genes |volume=11 |issue=2–3 |pages=285–297 |year=1995 |pmid=8828153|s2cid=20529415 }} ''(Comparison of the genomes of various T4-like phages)''
* Karam, J. D. ''et al.'' 1994. Molecular Biology of Bacteriophage T4. ASM Press, Washington, DC. ''(The second T4 bible, go here, as well as Mosig and Eiserling, 2006, to begin to learn about the biology T4 phage)'' {{ISBN|1-55581-064-0}}
* Eddy, S. R. 1992. Introns in the T-Even Bacteriophages. PhD thesis. University of Colorado at Boulder. ''(Chapter 3 provides overview of various T4-like phages as well as the isolation of then-new T4-like phages)''
* Surdis, T.J "et al" UC Santa Cruz, Nov 1978, "Bacteriophage attachment methods specific to T4", analysis, Overview.
* Mathews, C. K., E. M. Kutter, G. Mosig, and P. B. Berget. 1983. Bacteriophage T4. American Society for Microbiology, Washington, DC. ''(The first T4 bible; not all information here is duplicated in Karam ''et al.'', 1994; see especially the introductory chapter by Doermann for a historical overview of the T4-like phages)'' {{ISBN|0-914826-56-5}}
* Russell, R. L. 1967. Speciation Among the T-Even Bacteriophages. PhD thesis. California Institute of Technology. ''(Isolation of the RB series of T4-like phages)''
* {{cite journal | vauthors=Malys N, Nivinskas R | title = Non-canonical RNA arrangement in T4-even phages: accommodated ribosome binding site at the gene 26-25 intercistronic junction |journal = Mol Microbiol |volume = 73 | issue = 6 | pages = 1115–1127 | year = 2009 | pmid = 19708923 | doi =10.1111/j.1365-2958.2009.06840.x | doi-access = | s2cid = 8187771 }} ''(rare type of translational regulation characterized in T4)''
* {{cite journal |author=Kay D. |author2=Fildes P. |title=Hydroxymethylcytosine-containing and tryptophan-dependent bacteriophages isolated from city effluents |journal=J. Gen. Microbiol. |volume=27 |pages=143–6 |year=1962 |pmid=14454648 |doi=10.1099/00221287-27-1-143|doi-access=free }} ''(T4-like phage isolation, including that of phage Ox2)''
{{refend}}

==External links==
* [http://www.expasy.org/viralzone/all_by_species/504.html '''Viralzone''': T4-like viruses]
* [https://www.youtube.com/watch?v=V73nEGXUeBY Animation of T4 Bacteriophage Infecting E.coli]
* [https://www.youtube.com/watch?v=RbL3BZCGPA4 Animation of T4 Bacteriophage DNA packaging]

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{{DEFAULTSORT:Enterobacteria Phage T4}}
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Escherichia virus T4