Myxoma virus
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Classification: ICTVdB Virus Code: 00.058.1.05.001. Virus accession number: 58105001. Obsolete virus code: 58.1.5.0.001; superceded accession number: 58150001. NCBI Taxon Identifier NCBI Taxonomy ID: 10273. Type of the genus: 00.058.1.05. [1]poripoxvirus]|Leporipoxvirus subfamily 00.058.1. [Chordopoxvirinae]|[2] in the family 00.058. Poxviridae.]
Image: none found.
Higher Order Taxa: Viruses: Group I dsDNA viruses, no RNA stage; Family: Poxviridae; SubFamily: Chordopoxvirinae; Leporipoxvirus; Genus: Leporipoxvirus, Species: Myxoma virus
Genus species Image: none available given copyright restrictions.
Description and significance: Myxoma virions have two complex structures having either an envelope or no envelope, a surface membrane, a core, and lateral bodies. The envelope contains host-derived lipids and self-synthesized glycolipids. In the course of its life cycle, these virions produce both extracellular and intracellular particles. They can have two phenotypes and may be enveloped during their extracellular phase. The extracellular virions initiate viral infection. Myxoma virions may be segregated within non-occluded inclusion bodies. Typically they contain one enveloped nucleocapsid and are slightly pleomorphic, brick–shaped, and measure approximately 250 nm in diameter, 250–300 nm in length, and 200 nm in height. The core is biconcave with two lateral bodies, nested between either the core membrane or the surface membrane. They mature by budding through the membrane of the host cell. The Myxoma virus was important enough to have its genome sequenced is because it encodes multiple gene products designed to circumvent the host's cellular immune response to the viral infection, thereby inducing extensive immunosuppression in infected rabbits.
Natural Host: Domain Eucarya, Kingdom Animalia, Phylum Chordata, Subphylum Vertebrata, Class Mammalia, Order Lagomorphia, purportedly just "Oryctolagus cuniculus".
How and where it was isolated: The Lausanne strain of the virus was isolated by a team of Canadian scientists at the Department of Microbiology, The University of Western Ontario, London, Ontario, Canada. However, only a partial sequencing of the California MSW strain was achieved by a team associated with School of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, Australia. There they cloned EcoRI and SalI restriction fragments of viral DNA and sequenced the ends.
Genome structure Describe the size and content of the genome. REWORD. The DNA is fully sequenced. Sequence has the accession number [M93049]. The genome is not segmented and consists of a single molecule of linear double-stranded DNA. The complete genome is 161,773 nucleotides long with a central region containing highly conserved enzymatic and structural genes required for essential viral functions. However, the peripheral regions within the inverted terminal repeats at both ends of the genome encode nonessential factors that affect host response to infection. These factors include serine proteinase inhibitors, such as SERP1, Serp2, and Serp3, and a scrapin. All of these are located near the right end of the genome. They are responsible for major histo-compatibility complex class I down regulation. Additionally, the genome has a guanine + cytosine content of approximately 40%e and has terminal sequences with cross-linked hairpin ends forming one continuous polynucleotide chain. Moreover, these redundant sequences which have reiterated inverted terminal sequences that are tandemly repeated. Myxomatosis in European rabbits is a severely debilitating disease characterized by profound systemic cellular immunosuppression and a high rate of mortality. The causative agent, myxoma virus, is a member of the poxvirus family and prototype of the Leporipoxvirus genus. As a major step toward defining the genetic strategies by which the virus circumvents host antiviral responses, the genomic DNA sequence of myxoma virus, strain Lausanne, was determined. A total of 171 open reading frames were assigned to cover the 161.8-kb genome, including two copies each of the 12 genes that map within the 11.5-kb terminal inverted repeats. Database searches revealed a central core of approximately 120 kb that encodes more than 100 genes that exhibit close relationships to the conserved genes of members of other poxvirus genera. Open reading frames with predicted signal sequences, localization motifs, or homology to known proteins with immunomodulatory or host-range functions were examined more extensively for predicted features such as hydrophobic regions, nucleic acid binding domains, ankyrin repeats, serpin signatures, lectin domains. and structural cysteine spacings. As a result, several novel, potentially immunomodulatory proteins have been identified, including a family with multiple ankyrin-repeat domains, an OX-2 like member of the neural cell adhesion molecule family, a third myxoma serpin, a putative chemokine receptor fragment, two natural killer receptor-like species, and a variety of species with domains closely related to diverse host immune regulatory proteins. Coupled with the genomic sequencing of the related leporipoxvirus Shope fibroma virus, this work affirms the existence of a conserved complement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxvirus family member to counter the immune responses of the infected host. [Cheryl Cameron et al. "The Complete DNA Sequence of Myxoma Virus." Virology, Volume 264, Issue 2, 25 November 1999, Pages 298-318].
Interesting Features Myxoma virus subverts the host immune response using two distinct viral mechanisms delivered by viral proteins. First the virus produces virus-encoded proteins known as viroceptors or virokines that mimic host receptors or cytokines. These act to block extracellular immune signals thereby providing effective clearance and producing a virus friendly environment. Secondly, the virus uses intracellular viral proteins to retard the innate antiviral responses such as apoptosis, and to thwart an infected cell's mechanisms to communicate with its immune system.
and/or cell structures; how it gains energy; what important molecules it produces.
Ecology [edit]
Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc. Pathology [edit]
How does this organism cause disease? REWORD Myxoma virus (MV) is a poxvirus and the prototypic member of the Leporipoxvirus genus. MV is the causative agent of myxomatosis, a lethal and deblilitating disease of European rabbits (Oryctolagus cuniculus), characterized by profound systemic immunosuppression (11, 12). myxoma virus encodes multiple proteins capable of downregulating the host innate and acquired immune responses. Other virus-encoded proteins enable replication in host lymphocytes and monocytes, for example, by inhibiting apoptosis. Specifically, Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a serine proteinase inhibitor (serpin). Virulence may instead depend on inhibition of proinflammatory proteinases by SERP2.
Despite the increasingly detailed molecular knowledge of myxoma virus, relatively little is known about the dynamics of the interaction of the virus with the integrated host-immune system during infection
What makes it biologically interesting?
The M128L myxoma virus gene expresses a five-membrane spanning cell surface protein that has amino acid homology to cellular CD47 proteins. CD47 is associated with leukocyte adhesion, motility, activation, and phagocytosis. M128L is necessary for the production of a lethal infection in susceptible rabbits. However it is not essential for the dissemination of virus within the host. The M128L protein is a novel CD47-like immunomodulatory gene of myxoma virus required for full pathogenesis of the virus in the European rabbit.
Human, animal, plant hosts? Virulence factors, as well as patient symptoms. Application to Biotechnology [edit]
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Does this organism produce any useful compounds or enzymes? What are they and how are they used? Current Research [edit]
Enter summaries of the most recent research here--at least three required References [edit]