Murine leukemia virus

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Murine leukemia virus
Virus classification OOjs UI icon edit-ltr.svg
(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.

Contents

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.[ 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

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

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

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

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

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

Related Research Articles

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Reverse transcriptase</span> Enzyme which generates DNA

A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible.

Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus Betaretrovirus. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by John Joseph Bittner while working at the Jackson Laboratory in Bar Harbor, Maine. Bittner established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk. The majority of mammary tumors in mice are caused by mouse mammary tumor virus.

Metaviridae is a family of viruses which exist as Ty3-gypsy LTR retrotransposons in a eukaryotic host's genome. They are closely related to retroviruses: members of the family Metaviridae share many genomic elements with retroviruses, including length, organization, and genes themselves. This includes genes that encode reverse transcriptase, integrase, and capsid proteins. The reverse transcriptase and integrase proteins are needed for the retrotransposon activity of the virus. In some cases, virus-like particles can be formed from capsid proteins.

<span class="mw-page-title-main">Viral replication</span> Formation of biological viruses during the infection process

Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.

Lentivirus is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lentiviruses are distributed worldwide, and are known to be hosted in apes, cows, goats, horses, cats, and sheep as well as several other mammals.

<i>Gammaretrovirus</i> Genus of viruses

Gammaretrovirus is a genus in the Retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds.

<span class="mw-page-title-main">Endogenous retrovirus</span> Inherited retrovirus encoded in an organisms genome

Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<i>Jaagsiekte sheep retrovirus</i> Species of virus

Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep, called ovine pulmonary adenocarcinoma.

Rous sarcoma virus (RSV) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.

Env is a viral gene that encodes the protein forming the viral envelope. The expression of the env gene enables retroviruses to target and attach to specific cell types, and to infiltrate the target cell membrane.

Koala retrovirus (KoRV) is a retrovirus that is present in many populations of koalas. It has been implicated as the agent of koala immune deficiency syndrome (KIDS), an AIDS-like immunodeficiency that leaves infected koalas more susceptible to infectious disease and cancers. The virus is thought to be a recently introduced exogenous virus that is also integrating into the koala genome. Thus the virus can transmit both horizontally and vertically. The horizontal modes of transmission are not well defined but are thought to require close contact.

Retroviral matrix proteins are components of envelope-associated capsids of retroviruses. These proteins line the inner surface of viral envelopes and are associated with viral membranes.

Mason-Pfizer monkey virus (M-PMV), formerly Simian retrovirus (SRV), is a species of retroviruses that usually infect and cause a fatal immune deficiency in Asian macaques. The ssRNA virus appears sporadically in mammary carcinoma of captive macaques at breeding facilities which expected as the natural host, but the prevalence of this virus in feral macaques remains unknown. M-PMV was transmitted naturally by virus-containing body fluids, via biting, scratching, grooming, and fighting. Cross contaminated instruments or equipment (fomite) can also spread this virus among animals.

An endogenous viral element (EVE) is a DNA sequence derived from a virus, and present within the germline of a non-viral organism. EVEs may be entire viral genomes (proviruses), or fragments of viral genomes. They arise when a viral DNA sequence becomes integrated into the genome of a germ cell that goes on to produce a viable organism. The newly established EVE can be inherited from one generation to the next as an allele in the host species, and may even reach fixation.

Bovine foamy virus (BFV) is a ss(+)RNA retrovirus that belongs to the genus spumaviridae. Spumaviruses differ from the other six members of family retroviridae, both structurally and in pathogenic nature. Spumaviruses derive their name from spuma the latin for "foam". The 'foam' aspect of 'foamy virus' comes from syncytium formation and the rapid vacuolization of infected cells, creating a 'foamy' appearance.

Feline foamy virus or Feline syncytial virus is a retrovirus and belongs to the family Retroviridae and the subfamily Spumaretrovirinae. It shares the genus Felispumavirus with only Puma feline foamy virus. There has been controversy on whether FeFV is nonpathogenic as the virus is generally asymptomatic in affected cats and does not cause disease. However, some changes in kidney and lung tissue have been observed over time in cats affected with FeFV, which may or may not be directly affiliated. This virus is fairly common and infection rates gradually increase with a cat's age. Study results from antibody examinations and PCR analysis have shown that over 70% of felines over 9 years old were seropositive for Feline foamy virus. Viral infections are similar between male and female domesticated cats whereas in the wild, more feral females cats are affected with FeFV.

Gibbon-ape leukemia virus (GaLV) is an oncogenic, type C retrovirus that has been isolated from primate neoplasms, including the white-handed gibbon and woolly monkey. The virus was identified as the etiological agent of hematopoietic neoplasms, leukemias, and immune deficiencies within gibbons in 1971, during the epidemic of the late 1960s and early 1970s. Epidemiological research into the origins of GaLV has developed two hypotheses for the virus' emergence. These include cross-species transmission of the retrovirus present within a species of East Asian rodent or bat, and the inoculation or blood transfusion of a MbRV-related virus into captured gibbons populations housed at medical research institutions. The virus was subsequently identified in captive gibbon populations in Thailand, the US and Bermuda.

References

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Further reading