Murine leukemia virus
|Murine leukemia virus|
|Group:||Group VI (ssRNA-RT)|
|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.
The murine leukemia viruses are 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 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.
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 genomes 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 proteins, 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.
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.
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.
Applications of MLVs
- 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 used in Biotechnology
- Stoye, J. P.; Coffin, J. M. (1987). "The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination". Journal of Virology 61 (9): 2659–2669. PMC 255766. PMID 3039159.
- Coffin, J. M.; Stoye, J. P.; Frankel, W. N. (1989). "Genetics of endogenous murine leukemia viruses". Annals of the New York Academy of Sciences 567: 39–49. Bibcode:1989NYASA.567...39C. doi:10.1111/j.1749-6632.1989.tb16457.x. PMID 2552892.
- Stoye, JP; Moroni, C; Coffin, JM (1991). "Virological events leading to spontaneous AKR thymomas". Journal of Virology 65 (3): 1273–85. PMC 239902. PMID 1847454.
- D'Souza V, Dey A, Habib D, Summers MF (2004). "NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus". J Mol Biol 337 (2): 427–42. doi:10.1016/j.jmb.2004.01.037. PMID 15003457.
- D'Souza V, Summers MF (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.
- Voisin, V.; Rassart, E. (2007). "Complete genome sequences of the two viral variants of the Graffi MuLV: phylogenetic relationship with other murine leukemia retroviruses". Virology 361 (2): 335–347. doi:10.1016/j.virol.2006.10.045. PMID 17208267.
- Skasko, M.; Weiss, K.; Reynolds, H.; Jamburuthugoda, V.; Lee, K.; Kim, B. (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): 12190–12200. doi:10.1074/jbc.M412859200. PMC 1752212. PMID 15644314.
- A comparison of MLV vectors with other clinical gene transfer vectors
- Murine leukemia virus (MLV) replication monitored with fluorescent proteins