Murine leukemia virus
Encyclopedia
The murine leukemia viruses (MLVs or MuLVs) are retrovirus
es 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
.
genus of the Retroviridae family. The viral particles of replicating MLVs have C-type morphology
as determined by electron microscopy
.
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.
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. The ecotropic MLVs (from eco, "house") are capable of infecting mouse cells in culture. Non-ecotropic MLVs may be xenotropic (from xeno, "foreign", infecting non-mouse species), polytropic or modified polytropic (infecting a range of hosts including mice). Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of recombination
of endogenous sequences.
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 membrane. The lipid bilayer contains integrated host and viral proteins studded with carbohydrate
molecules. The viral particle is approximately 90 nanometres (nm) in diameter.
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 gag
, pol
, and 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' poly-adenosine
tail.
The genome includes a conserved RNA structural element called a core encapsidation signal
that directs packaging of RNA into the virion; the tertiary structure of this element has been solved using nuclear magnetic resonance spectroscopy
.
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es named for their ability to cause cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
in murine
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
(mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses
Endogenous retrovirus
Endogenous retroviruses are sequences in the genome thought to be derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome....
. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of reverse transcription
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
.
Classification
The murine leukemia viruses are Type VI retroviruses belonging to the gammaretroviralGammaretrovirus
A gammaretrovirus is a genus of the retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus.Many endogenous retroviruses, closely related to exogenous gammaretroviruses, are present in the DNA of mammals , birds, reptiles and amphibians.Many of the...
genus of the Retroviridae family. The viral particles of replicating MLVs have C-type morphology
Morphology (biology)
In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....
as determined by electron microscopy
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
.
The MLVs include both exogenous and endogenous viruses. Exogenous forms are transmitted as new infections from one host to another
Horizontal transmission
Horizontal transmission is the transmission of a bacterial, fungal, or viral infection between members of the same species that are not in a parent-child relationship....
. The Moloney, Rauscher, Abelson
Abelson murine leukemia virus
The Abelson murine leukemia virus is a retrovirus used to induce transformation of murine lymphoid cells. As a retrovirus, it has a single-stranded, positive sense RNA genome which replicates via a DNA intermediate mediated by a reverse transcriptase. The Abelson murine leukemia virus is named...
and Friend
Friend virus
The Friend virus is a strain of murine leukemia virus identified by Charlotte Friend in 1956. The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive retrovirus. The Friend virus has been used for both...
MLVs, named for their discoverers, are used in cancer research.
Endogenous MLVs are integrated
Pre-integration complex
The pre-integration complex is a nucleoprotein complex of viral genetic material and associated viral and host proteins. The PIC forms after uncoating of a viral particle after entry into the host cell...
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. The ecotropic MLVs (from eco, "house") are capable of infecting mouse cells in culture. Non-ecotropic MLVs may be xenotropic (from xeno, "foreign", infecting non-mouse species), polytropic or modified polytropic (infecting a range of hosts including mice). Different strains of mice may have different numbers of endogenous retroviruses, and new viruses may arise as the result of recombination
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
of endogenous sequences.
Virion structure
As Type C retrovirusRetrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
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
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
derived from the host cell membrane. The lipid bilayer contains integrated host and viral proteins studded with carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
molecules. The viral particle is approximately 90 nanometres (nm) in diameter.
Genome
The genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s of exogenous and endogenous murine leukemia viruses have been fully sequenced. The viral genome is a single stranded, linear, positive-sense RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecule of around 8000 nucleotides. From 5' to 3' (typically displayed as "left" to "right"), the genome contains gag
Group-specific antigen
Group-specific antigen is the genetic material that codes for the core structural proteins of a retrovirus.It comprises part of the gag-onc fusion protein.-Gag in HIV:...
, pol
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
, and env
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
regions, coding for structural proteins, enzymes including the RNA-dependent DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
(reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
), and coat protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, respectively. The genomic molecule contains a 5' methylated cap structure and a 3' poly-adenosine
Polyadenylation
Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...
tail.
The genome includes a conserved RNA structural element called a core encapsidation signal
Gammaretrovirus core encapsidation signal
The Gammaretrovirus core encapsidation signal is an RNA element known to be essential for stable dimerisation and efficient genome packaging during virus assembly. Dimerisation of the viral RNA genomes is proposed to act as an RNA conformational switch which exposes conserved UCUG elements and...
that directs packaging of RNA into the virion; the tertiary structure of this element has been solved using nuclear magnetic resonance spectroscopy
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
.
Viral evolution
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. MLV reverse transcriptases are thought to have a slightly higher fidelity than the HIV-1 RT.Applications of MLVs
- Gene therapyGene therapyGene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
: MLV-derived particles can deliver therapeutic genes to target cells. - CancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
studies: MLVs are used to study cancer developmentCarcinogenesisCarcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
. - As a model retrovirus in viral clearance studies
- Reverse Transcriptase from MMLV used in Biotechnology