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{{Short description|Species of virus}}
:''"MMLV" redirects here. It is also the [[Roman numeral]] for [[2055]].''
{{redirect|MMLV|the [[Roman numeral]]|2055}}
{{Taxobox
{{virusbox
<!-- Color parameter is not needed -- automatically assigned -->
⚫
| parent = Gammaretrovirus
| name = ''Murine leukemia virus''
| species = Murine leukemia virus
| virus_group = vi
| ordo = ''Unassigned''
| familia = ''[[Retroviridae]]''
| subfamilia = ''[[Orthoretrovirinae]]''
⚫
| genus = ''[[Gammaretrovirus]]''
| species = '''''Murine leukemia virus'''''
}}
}}
The '''murine leukemia viruses''' ('''MLVs''' or '''MuLVs''') are [[retrovirus]]es named for their ability to cause [[cancer]] in [[Murinae|murine]] (mouse) hosts. Some MLVs may infect other [[vertebrates]]. MLVs include both [[Retrovirus#Exogenous|exogenous]] and [[Endogenous retrovirus|endogenous viruses]]. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of [[Reverse transcriptase|reverse transcription]].
The '''murine leukemia viruses''' ('''MLVs''' or '''MuLVs''') are [[retrovirus]]es named for their ability to cause [[cancer]] in [[Murinae|murine]] (mouse) hosts. Some MLVs may infect other [[vertebrates]]. MLVs include both [[Retrovirus#Exogenous|exogenous]] and [[Endogenous retrovirus|endogenous viruses]]. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of [[Reverse transcriptase|reverse transcription]].


==Classification==
==Classification==
The murine leukemia viruses are [[Retrovirus#Group VI viruses|group/type VI retroviruses]] belonging to the [[Gammaretrovirus|gammaretroviral]] genus of the [[Retroviridae]] family. The viral particles of replicating MLVs have C-type [[morphology (biology)|morphology]] as determined by [[Electron microscope|electron microscopy]].
The murine leukemia viruses are [[Retrovirus#Group VI viruses|group/type VI retroviruses]] belonging to the [[Gammaretrovirus|gammaretroviral]] genus of the [[Retroviridae]] family. The viral particles of replicating MLVs have C-type [[morphology (biology)|morphology]] as determined by [[Electron microscope|electron microscopy]].{{cn|date=November 2022}}


The MLVs include both exogenous and endogenous viruses. Exogenous forms are transmitted as new infections from [[Horizontal transmission|one host to another]]. The [[Moloney virus|Moloney]], [[Rauscher virus|Rauscher]], [[Abelson murine leukemia virus|Abelson]] and [[Friend virus|Friend]] MLVs, named for their discoverers, are used in cancer research.
The MLVs include both exogenous and endogenous viruses. Exogenous forms are transmitted as new infections from [[Horizontal transmission|one host to another]]. The [[Moloney virus|Moloney]], [[Rauscher virus|Rauscher]], [[Abelson murine leukemia virus|Abelson]] and [[Friend virus|Friend]] MLVs, named for their discoverers, are used in cancer research.{{cn|date=November 2022}}


Endogenous MLVs are [[Pre-integration complex|integrated]] into the host's germ line and are passed from one generation to the next. Stoye and Coffin have classified them into four categories by host specificity, determined by the genomic sequence of their envelope region.<ref>{{cite journal | vauthors = Stoye JP, Coffin JM | title = The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination | journal = Journal of Virology | volume = 61 | issue = 9 | pages = 2659–69 | date = September 1987 | pmid = 3039159 | pmc = 255766 | doi = 10.1128/JVI.61.9.2659-2669.1987 }}</ref> The ''ecotropic'' MLVs (from Gr.''eco'', "Home") are capable of infecting mouse cells in culture. ''Non-ecotropic'' MLVs may be ''xenotropic'' (from ''xenos'', "foreign", infecting non-mouse species), ''polytropic'' or ''modified polytropic'' (infecting a range of hosts including mice). Among the latter MLVs are amphotropic viruses (Gr. amphos, "both") that can infect both mouse cells and cells of other animal species. These terms and descriptions for the MLV biologic classification were initially introduced by Levy.<ref name="pmid77206">{{cite book | vauthors = Levy JA | title = Modern Aspects of Electrochemistry | chapter = Xenotropic Type C Viruses | series = Current Topics in Microbiology and Immunology | volume = 79 | pages = 111–213 | date = 1978 | pmid = 77206 | doi = 10.1007/978-3-642-66853-1_4 | isbn = 978-1-4612-9003-2 }}</ref> Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of [[genetic recombination|recombination]] of endogenous sequences.<ref>{{cite journal | vauthors = Coffin JM, Stoye JP, Frankel WN | title = Genetics of endogenous murine leukemia viruses | journal = Annals of the New York Academy of Sciences | volume = 567 | issue = 1 | pages = 39–49 | year = 1989 | pmid = 2552892 | doi = 10.1111/j.1749-6632.1989.tb16457.x | bibcode = 1989NYASA.567...39C | s2cid = 28184389 }}</ref><ref>{{cite journal | vauthors = Stoye JP, Moroni C, Coffin JM | title = Virological events leading to spontaneous AKR thymomas | journal = Journal of Virology | volume = 65 | issue = 3 | pages = 1273–85 | date = March 1991 | pmid = 1847454 | pmc = 239902 | doi = 10.1128/JVI.65.3.1273-1285.1991 }}</ref>
Endogenous MLVs are [[Pre-integration complex|integrated]] into the host's germ line and are passed from one generation to the next. Stoye and Coffin have classified them into four categories by host specificity, determined by the genomic sequence of their envelope region.<ref>{{Cite journal
| pmid = 3039159
| year = 1987
| last1 = Stoye | first1 = J. P.
| last2 = Coffin | first2 = J. M.
| title = The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination
| volume = 61
| issue = 9
| pages = 2659–69
| pmc = 255766
| journal = Journal of Virology
}}</ref> The ''ecotropic'' MLVs (from Gr.''eco'', "Home") are capable of infecting mouse cells in culture. ''Non-ecotropic'' MLVs may be ''xenotropic'' (from ''xenos'', "foreign", infecting non-mouse species), ''polytropic'' or ''modified polytropic'' (infecting a range of hosts including mice). Among the latter MLVs are amphotropic viruses (Gr. amphos, "both") that can infect both mouse cells and cells of other animal species. These terms and descriptions for the MLV biologic classification were initially introduced by Levy.<ref>Levy, J.A., Xenotropic type C viruses. Current Topics in Microbiology and Immunology, 1978. 79: p. 111-213.</ref> Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of [[genetic recombination|recombination]] of endogenous sequences.<ref>{{Cite journal
| pmid = 2552892
| year = 1989
| last1 = Coffin | first1 = J. M.
| last2 = Stoye | first2 = J. P.
| last3 = Frankel | first3 = W. N.
| title = Genetics of endogenous murine leukemia viruses
| volume = 567
| pages = 39–49
| journal = Annals of the New York Academy of Sciences
| doi = 10.1111/j.1749-6632.1989.tb16457.x
|bibcode = 1989NYASA.567...39C }}</ref><ref>{{Cite journal
| pmid = 1847454
| year = 1991
| last1 = Stoye
| first1 = JP
| last2 = Moroni
| first2 = C
| last3 = Coffin
| first3 = JM
| title = Virological events leading to spontaneous AKR thymomas
| volume = 65
| issue = 3
| pages = 1273–85
| pmc = 239902
| journal = Journal of Virology
}}</ref>


==Virion structure==
==Virion structure==
As Type C [[retrovirus]]es, replicating murine leukemia viruses produce a virion containing a spherical [[nucleocapsid]] (the viral genome in complex with viral proteins) surrounded by a [[lipid bilayer]] derived from the host cell [[Plasma membrane|membrane]]. The lipid bilayer contains integrated host and viral proteins studded with [[carbohydrate]] [[molecules]]. The viral particle is approximately 90 [[nanometres]] (nm) in diameter. The viral glycoproteins are expressed on the membrane as trimer of a precursor Env, which is cleaved into SU and TM by host furin or furin-like proprotein convertases. This cleavage is essential for the Env incorporation into virus particles.<ref>{{cite journal|last1=Apte|first1=Swapna|last2=Sanders|first2=David Avram|title=Effects of retroviral envelope-protein cleavage upon trafficking, incorporation, and membrane fusion|journal=Virology|date=September 2010|volume=405|issue=1|pages=214–224|doi=10.1016/j.virol.2010.06.004|url=http://www.sciencedirect.com/science/article/pii/S0042682210003855}}</ref>
As Type C [[retrovirus]]es, replicating murine leukemia viruses produce a virion containing a spherical [[nucleocapsid]] (the viral genome in complex with viral proteins) surrounded by a [[lipid bilayer]] derived from the host cell [[Plasma membrane|membrane]]. The lipid bilayer contains integrated host and viral proteins studded with [[carbohydrate]] [[molecules]]. The viral particle is approximately 90 [[nanometres]] (nm) in diameter. The viral glycoproteins are expressed on the membrane as trimer of a precursor Env, which is cleaved into SU and TM by host furin or furin-like proprotein convertases. This cleavage is essential for the Env incorporation into virus particles.<ref>{{cite journal | vauthors = Apte S, Sanders DA | title = Effects of retroviral envelope-protein cleavage upon trafficking, incorporation, and membrane fusion | journal = Virology | volume = 405 | issue = 1 | pages = 214–24 | date = September 2010 | pmid = 20591459 | doi = 10.1016/j.virol.2010.06.004 | doi-access = }}</ref>


==Genome== Retro Virus
==Genome==
The [[genome]]s of exogenous and endogenous murine leukemia viruses have been fully sequenced. The viral genome is a single stranded, linear, positive-sense [[RNA]] molecule of around 8000 nucleotides. From 5' to 3' (typically displayed as "left" to "right"), the genome contains ''[[Group-specific antigen|gag]]'', ''[[Polymerase|pol]]'', and ''[[Viral envelope|env]]'' regions, coding for structural proteins, enzymes including the RNA-dependent [[DNA polymerase]] ([[reverse transcriptase]]), and coat [[protein]]s, respectively. The genomic molecule contains a 5' methylated cap structure and a 3' [[Polyadenylation|poly-adenosine]] tail.
The [[genome]]s of exogenous and endogenous murine leukemia viruses have been fully sequenced. The viral genome is a single stranded, positive-sense [[RNA]] highly folded, molecule of around 8000 nucleotides. From 5' to 3' (typically displayed as "left" to "right"), the genome contains ''[[Group-specific antigen|gag]]'', ''[[Polymerase|pol]]'', and ''[[Viral envelope|env]]'' regions, coding for structural proteins, enzymes including the RNA-dependent [[DNA polymerase]] ([[reverse transcriptase]]), and coat [[protein]]s, respectively. In addition to these three polyproteins: Gag, Pol and Env, common to all retroviruses, MLV also produces the p50/p60 proteins issued from an alternative splicing of its genomic RNA..<ref name="pmid12970198">{{cite journal | vauthors = Houzet L, Battini JL, Bernard E, Thibert V, Mougel M | title = A new retroelement constituted by a natural alternatively spliced RNA of murine replication-competent retroviruses | journal = The EMBO Journal | volume = 22 | issue = 18 | pages = 4866–75 | date = September 2003 | pmid = 12970198 | pmc = 212718 | doi = 10.1093/emboj/cdg450 }}</ref> The genomic molecule contains a 5' methylated cap structure and a 3' [[Polyadenylation|poly-adenosine]] tail.{{cn|date=November 2022}}


The genome includes a conserved RNA structural element called a [[Gammaretrovirus core encapsidation signal|core encapsidation signal]] that directs packaging of RNA into the virion; the tertiary structure of this element has been solved using [[NMR spectroscopy|nuclear magnetic resonance spectroscopy]].<ref name="pmid15003457">{{cite journal |doi=10.1016/j.jmb.2004.01.037 |vauthors=D'Souza V, Dey A, Habib D, Summers MF |title=NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus |journal=J Mol Biol |volume=337 |issue=2 |pages=427–42 |year=2004 |pmid=15003457}}</ref><ref name="pmid15457265">{{cite journal |doi=10.1038/nature02944 |vauthors=D'Souza V, Summers MF |title=Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus |journal=Nature |volume=431 |issue=7008 |pages=586–90 |year=2004 |pmid=15457265|bibcode = 2004Natur.431..586D }}</ref>
The genome includes a conserved RNA structural element called a [[Gammaretrovirus core encapsidation signal|core encapsidation signal]] that directs packaging of RNA into the virion;<ref name="pmid9311905">{{cite journal | vauthors = Mougel M, Barklis E | title = A role for two hairpin structures as a core RNA encapsidation signal in murine leukemia virus virions | journal = Journal of Virology | volume = 71 | issue = 10 | pages = 8061–5 | date = October 1997 | pmid = 9311905 | pmc = 192172 | doi = 10.1128/JVI.71.10.8061-8065.1997 }}</ref> the tertiary structure of this element has been solved using [[NMR spectroscopy|nuclear magnetic resonance spectroscopy]].<ref name="pmid15003457">{{cite journal | vauthors = D'Souza V, Dey A, Habib D, Summers MF | title = NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus | journal = Journal of Molecular Biology | volume = 337 | issue = 2 | pages = 427–42 | date = March 2004 | pmid = 15003457 | doi = 10.1016/j.jmb.2004.01.037 }}</ref><ref name="pmid15457265">{{cite journal | vauthors = D'Souza V, Summers MF | title = Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus | journal = Nature | volume = 431 | issue = 7008 | pages = 586–90 | date = September 2004 | pmid = 15457265 | doi = 10.1038/nature02944 | bibcode = 2004Natur.431..586D | s2cid = 4409362 }}</ref>

== Replication cycle ==
Infection begins when the surface glycoprotein (SU) on the outer part of the mature, infectious virion binds to the receptor on the surface of the new host cell. As a result of attachment, changes occur in Env. These changes lead to the release of the surface glycoprotein (SU) and the conformational rearrangement of the transmembrane protein (TM). As a result, the fusion of the viral membrane and the plasma membrane occurs. Fusion of the membranes leads to the deposition of the virion content in the cytoplasm of the cell. After entering the cytoplasm, viral RNA is copied into a single dsDNA molecule by reverse transcriptase. This DNA is somehow carried into the nucleus, where the integrase (IN) protein catalyzes its insertion into chromosomal DNA. The viral DNA integrated into the host genome is called “provirus”. It is copied and translated by normal host-cell machinery. The encoded proteins are trafficked to the plasma membrane, where they assemble into progeny virus particles. Immature particles are released from the cell with the help of cellular "ESCRT" machinery and then they undergo maturation as the viral protease cleaves the polyproteins. The particle cannot start a new infection until maturation occurs.<ref>{{cite journal | vauthors = Rein A | title = Murine leukemia viruses: objects and organisms | journal = Advances in Virology | volume = 2011 | pages = 403419 | date = 2011 | pmid = 22312342 | pmc = 3265304 | doi = 10.1155/2011/403419 | doi-access = free }}</ref>


==Viral evolution==
==Viral evolution==
As with other retroviruses, the MLVs replicate their genomes with relatively low fidelity. Thus, [[Quasispecies#Application to biological research|divergent viral sequences]] may be found in a single host organism.<ref>{{Cite journal| volume = 361| title = Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses| issue = 2| pages = 335–347| journal = Virology | first2 = E.| last2 = Rassart| pmid = 17208267| year = 2007| last1 = Voisin | first1 = V.| doi = 10.1016/j.virol.2006.10.045 }}</ref> MLV reverse transcriptases are thought to have a slightly higher fidelity than the HIV-1 RT.<ref>{{Cite journal
As with other retroviruses, the MLVs replicate their genomes with relatively low fidelity. Thus, [[Quasispecies#Application to biological research|divergent viral sequences]] may be found in a single host organism.<ref>{{cite journal | vauthors = Voisin V, Rassart E | title = Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses | journal = Virology | volume = 361 | issue = 2 | pages = 335–47 | date = May 2007 | pmid = 17208267 | doi = 10.1016/j.virol.2006.10.045 | doi-access = free }}</ref> MLV reverse transcriptases are thought to have a slightly higher fidelity than the HIV-1 RT.<ref>{{cite journal | vauthors = Skasko M, Weiss KK, Reynolds HM, Jamburuthugoda V, Lee K, Kim B | title = Mechanistic differences in RNA-dependent DNA polymerization and fidelity between murine leukemia virus and HIV-1 reverse transcriptases | journal = The Journal of Biological Chemistry | volume = 280 | issue = 13 | pages = 12190–200 | date = April 2005 | pmid = 15644314 | pmc = 1752212 | doi = 10.1074/jbc.M412859200 | doi-access = free }}</ref>
| doi = 10.1074/jbc.M412859200
| pmid = 15644314
| year = 2005
| last1 = Skasko | first1 = M.
| last2 = Weiss | first2 = K.
| last3 = Reynolds | first3 = H.
| last4 = Jamburuthugoda | first4 = V.
| last5 = Lee | first5 = K.
| last6 = Kim | first6 = B.
| title = Mechanistic differences in RNA-dependent DNA polymerization and fidelity between murine leukemia virus and HIV-1 reverse transcriptases
| volume = 280
| issue = 13
| pages = 12190–200
| pmc = 1752212
| journal = The Journal of Biological Chemistry
}}</ref>


==MLV research==
==Research==
The [[Friend virus]] (FV) is a strain of murine leukemia virus. The Friend virus has been used for both immunotherapy and vaccines. Experiments have shown that it is possible to protect against Friend virus infection with several types of vaccines, including attenuated viruses, viral proteins, peptides, and recombinant vaccinia vectors expressing the Friend virus gene. In a study of vaccinated mice, it was possible to identify the immunological [[epitopes]] required for protection against the virus, thus determining the types of immunological responses necessary or required for protection against it. The research discovered protective epitopes that were localized to F-MuLV gag and env proteins. This was achieved using recombinant vaccinia viruses expressing the gag and env genes of FV.
The [[Friend virus]] (FV) is a strain of murine leukemia virus. The Friend virus has been used for both immunotherapy and vaccines. Experiments have shown that it is possible to protect against Friend virus infection with several types of vaccines, including attenuated viruses, viral proteins, peptides, and recombinant vaccinia vectors expressing the Friend virus gene. In a study of vaccinated mice, it was possible to identify the immunological [[epitopes]] required for protection against the virus, thus determining the types of immunological responses necessary or required for protection against it. The research discovered protective epitopes that were localized to F-MuLV gag and env proteins. This was achieved using recombinant [[vaccinia]] viruses expressing the gag and env genes of FV.


==Application==
==Application==
Line 90: Line 35:
* [[Cancer]] studies: MLVs are used to study [[Carcinogenesis|cancer development]].
* [[Cancer]] studies: MLVs are used to study [[Carcinogenesis|cancer development]].
* As a model retrovirus in viral clearance studies
* As a model retrovirus in viral clearance studies
* Reverse Transcriptase from MMLV used in Biotechnology
* Reverse transcriptase from MMLV is used in biotechnology


==References==
== References ==
{{Reflist}}
{{Reflist}}


== Further reading ==
==External links==
{{refbegin}}
{{refbegin}}
* {{cite journal |first=Jeremy W. |last=Fry |first2=Kathryn J. |last2=Wood |title=Gene therapy: potential applications in clinical transplantation |quote=[http://journals.cambridge.org/fulltext_content/ERM/ERM1_11/S1462399499000691sup002.htm Table 1. A comparison of vectors in use for clinical gene transfer] |journal=Expert Reviews in Molecular Medicine |pages=1–20 |date=8 June 1999 |pmid=14585123 |doi=10.1017/S1462399499000691 }}
* {{cite journal | vauthors = Wood KJ, Fry J | title = Gene therapy: potential applications in clinical transplantation | journal = Expert Reviews in Molecular Medicine | volume = 1999 | issue = 11 | pages = 1–20 | date = June 1999 | pmid = 14585123 | doi = 10.1017/S1462399499000691 | s2cid = 26836701 | quote = [http://journals.cambridge.org/fulltext_content/ERM/ERM1_11/S1462399499000691sup002.htm Table 1. A comparison of vectors in use for clinical gene transfer] }}
* {{cite journal |vauthors=Sliva K, Erlwein O, Bittner A, Schnierle BS |title=Murine leukemia virus (MLV) replication monitored with fluorescent proteins |journal=Virol. J. |volume=1 |issue= |pages=14 |year=2004 |pmid=15610559 |pmc=544597 |doi=10.1186/1743-422X-1-14 |url=http://virologyj.biomedcentral.com/articles/10.1186/1743-422X-1-14}}
* {{cite journal | vauthors = Sliva K, Erlwein O, Bittner A, Schnierle BS | title = Murine leukemia virus (MLV) replication monitored with fluorescent proteins | journal = Virology Journal | volume = 1 | pages = 14 | date = December 2004 | pmid = 15610559 | pmc = 544597 | doi = 10.1186/1743-422X-1-14 | doi-access = free }}
{{refend}}
{{refend}}


Latest revision as of 15:03, 6 April 2024

"MMLV" redirects here. For the Roman numeral, see 2055.
Murine leukemia virus
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Gammaretrovirus
Species:
Murine leukemia virus

The murine leukemia viruses (MLVs or MuLVs) are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of reverse transcription.

Classification[edit]

The murine leukemia viruses are group/type VI retroviruses belonging to the gammaretroviral genus of the Retroviridae family. The viral particles of replicating MLVs have C-type morphology as determined by electron microscopy.[citation needed]

The MLVs include both exogenous and endogenous viruses. Exogenous forms are transmitted as new infections from one host to another. The Moloney, Rauscher, Abelson and Friend MLVs, named for their discoverers, are used in cancer research.[citation needed]

Endogenous MLVs are integrated into the host's germ line and are passed from one generation to the next. Stoye and Coffin have classified them into four categories by host specificity, determined by the genomic sequence of their envelope region.[1] The ecotropic MLVs (from Gr.eco, "Home") are capable of infecting mouse cells in culture. Non-ecotropic MLVs may be xenotropic (from xenos, "foreign", infecting non-mouse species), polytropic or modified polytropic (infecting a range of hosts including mice). Among the latter MLVs are amphotropic viruses (Gr. amphos, "both") that can infect both mouse cells and cells of other animal species. These terms and descriptions for the MLV biologic classification were initially introduced by Levy.[2] Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of recombination of endogenous sequences.[3][4]

Virion structure[edit]

As Type C retroviruses, replicating murine leukemia viruses produce a virion containing a spherical nucleocapsid (the viral genome in complex with viral proteins) surrounded by a lipid bilayer derived from the host cell membrane. The lipid bilayer contains integrated host and viral proteins studded with carbohydrate molecules. The viral particle is approximately 90 nanometres (nm) in diameter. The viral glycoproteins are expressed on the membrane as trimer of a precursor Env, which is cleaved into SU and TM by host furin or furin-like proprotein convertases. This cleavage is essential for the Env incorporation into virus particles.[5]

Genome[edit]

The genomes of exogenous and endogenous murine leukemia viruses have been fully sequenced. The viral genome is a single stranded, positive-sense RNA highly folded, molecule of around 8000 nucleotides. From 5' to 3' (typically displayed as "left" to "right"), the genome contains gag, pol, and env regions, coding for structural proteins, enzymes including the RNA-dependent DNA polymerase (reverse transcriptase), and coat proteins, respectively. In addition to these three polyproteins: Gag, Pol and Env, common to all retroviruses, MLV also produces the p50/p60 proteins issued from an alternative splicing of its genomic RNA..[6] The genomic molecule contains a 5' methylated cap structure and a 3' poly-adenosine tail.[citation needed]

The genome includes a conserved RNA structural element called a core encapsidation signal that directs packaging of RNA into the virion;[7] the tertiary structure of this element has been solved using nuclear magnetic resonance spectroscopy.[8][9]

Replication cycle[edit]

Infection begins when the surface glycoprotein (SU) on the outer part of the mature, infectious virion binds to the receptor on the surface of the new host cell. As a result of attachment, changes occur in Env. These changes lead to the release of the surface glycoprotein (SU) and the conformational rearrangement of the transmembrane protein (TM). As a result, the fusion of the viral membrane and the plasma membrane occurs. Fusion of the membranes leads to the deposition of the virion content in the cytoplasm of the cell. After entering the cytoplasm, viral RNA is copied into a single dsDNA molecule by reverse transcriptase. This DNA is somehow carried into the nucleus, where the integrase (IN) protein catalyzes its insertion into chromosomal DNA. The viral DNA integrated into the host genome is called “provirus”. It is copied and translated by normal host-cell machinery. The encoded proteins are trafficked to the plasma membrane, where they assemble into progeny virus particles. Immature particles are released from the cell with the help of cellular "ESCRT" machinery and then they undergo maturation as the viral protease cleaves the polyproteins. The particle cannot start a new infection until maturation occurs.[10]

Viral evolution[edit]

As with other retroviruses, the MLVs replicate their genomes with relatively low fidelity. Thus, divergent viral sequences may be found in a single host organism.[11] MLV reverse transcriptases are thought to have a slightly higher fidelity than the HIV-1 RT.[12]

Research[edit]

The Friend virus (FV) is a strain of murine leukemia virus. The Friend virus has been used for both immunotherapy and vaccines. Experiments have shown that it is possible to protect against Friend virus infection with several types of vaccines, including attenuated viruses, viral proteins, peptides, and recombinant vaccinia vectors expressing the Friend virus gene. In a study of vaccinated mice, it was possible to identify the immunological epitopes required for protection against the virus, thus determining the types of immunological responses necessary or required for protection against it. The research discovered protective epitopes that were localized to F-MuLV gag and env proteins. This was achieved using recombinant vaccinia viruses expressing the gag and env genes of FV.

Application[edit]

  • Gene therapy: MLV-derived particles can deliver therapeutic genes to target cells.
  • Cancer studies: MLVs are used to study cancer development.
  • As a model retrovirus in viral clearance studies
  • Reverse transcriptase from MMLV is used in biotechnology

References[edit]

  1. ^ Stoye JP, Coffin JM (September 1987). "The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination". Journal of Virology. 61 (9): 2659–69. doi:10.1128/JVI.61.9.2659-2669.1987. PMC 255766. PMID 3039159.
  2. ^ Levy JA (1978). "Xenotropic Type C Viruses". Modern Aspects of Electrochemistry. Current Topics in Microbiology and Immunology. Vol. 79. pp. 111–213. doi:10.1007/978-3-642-66853-1_4. ISBN 978-1-4612-9003-2. PMID 77206.
  3. ^ Coffin JM, Stoye JP, Frankel WN (1989). "Genetics of endogenous murine leukemia viruses". Annals of the New York Academy of Sciences. 567 (1): 39–49. Bibcode:1989NYASA.567...39C. doi:10.1111/j.1749-6632.1989.tb16457.x. PMID 2552892. S2CID 28184389.
  4. ^ Stoye JP, Moroni C, Coffin JM (March 1991). "Virological events leading to spontaneous AKR thymomas". Journal of Virology. 65 (3): 1273–85. doi:10.1128/JVI.65.3.1273-1285.1991. PMC 239902. PMID 1847454.
  5. ^ Apte S, Sanders DA (September 2010). "Effects of retroviral envelope-protein cleavage upon trafficking, incorporation, and membrane fusion". Virology. 405 (1): 214–24. doi:10.1016/j.virol.2010.06.004. PMID 20591459.
  6. ^ Houzet L, Battini JL, Bernard E, Thibert V, Mougel M (September 2003). "A new retroelement constituted by a natural alternatively spliced RNA of murine replication-competent retroviruses". The EMBO Journal. 22 (18): 4866–75. doi:10.1093/emboj/cdg450. PMC 212718. PMID 12970198.
  7. ^ Mougel M, Barklis E (October 1997). "A role for two hairpin structures as a core RNA encapsidation signal in murine leukemia virus virions". Journal of Virology. 71 (10): 8061–5. doi:10.1128/JVI.71.10.8061-8065.1997. PMC 192172. PMID 9311905.
  8. ^ D'Souza V, Dey A, Habib D, Summers MF (March 2004). "NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus". Journal of Molecular Biology. 337 (2): 427–42. doi:10.1016/j.jmb.2004.01.037. PMID 15003457.
  9. ^ D'Souza V, Summers MF (September 2004). "Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus". Nature. 431 (7008): 586–90. Bibcode:2004Natur.431..586D. doi:10.1038/nature02944. PMID 15457265. S2CID 4409362.
  10. ^ Rein A (2011). "Murine leukemia viruses: objects and organisms". Advances in Virology. 2011: 403419. doi:10.1155/2011/403419. PMC 3265304. PMID 22312342.
  11. ^ Voisin V, Rassart E (May 2007). "Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses". Virology. 361 (2): 335–47. doi:10.1016/j.virol.2006.10.045. PMID 17208267.
  12. ^ Skasko M, Weiss KK, Reynolds HM, Jamburuthugoda V, Lee K, Kim B (April 2005). "Mechanistic differences in RNA-dependent DNA polymerization and fidelity between murine leukemia virus and HIV-1 reverse transcriptases". The Journal of Biological Chemistry. 280 (13): 12190–200. doi:10.1074/jbc.M412859200. PMC 1752212. PMID 15644314.

Further reading[edit]

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