Animation 225 Survey

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George Wells

ANIMATION

ANIMATION_225_SURVEY

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 ==

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.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 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.Different strains of mice may have

different numbers of endogenous retroviruses, and new viruses may arise as the result of
recombination of endogenous sequences.== Virion structure ==

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.== Genome ==

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..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.== 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.== 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.== 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.== Application

==
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 ==

== Further reading ==

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