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. [1]
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. [1]
Many endogenous retroviruses, closely related to exogenous gammaretroviruses, are present in the DNA of mammals (including humans), birds, reptiles and amphibians. [2] Many also share a conserved RNA structural element called a core encapsidation signal. [3]
The avian reticuloendotheliosis viruses are not strictly avian viruses—it appears that reticuloendotheliosis viruses are mammalian viruses that were accidentally introduced into birds in the 1930s during research on malaria. [4]
As a potential vector for gene therapy, gammaretroviruses have some advantages over HIV as a lentiviral vector. Specifically, the gammaretroviral packaging system does not require the incorporation of any sequences overlapping with coding sequences of gag, pol, or accessory genes. [5]
Gammaretroviruses have a wide range of implications for animals. They have been linked with several diseases including cancer, specifically leukemias and lymphomas, various neurological diseases, and some immunodeficiencies in many different species. Gammaretroviruses are similar to other retroviruses and reverse transcribe a positive single strand RNA into double stranded DNA. The double stranded DNA is highly stable and easily integrated into a host genome. A few examples of the virus are Moloney murine leukemia virus, xenotropic MuLB-related virus, feline leukemia virus, and feline sarcoma virus. [6] [7] [8]
Gammaretroviruses are very popular retroviral vectors in laboratory studies. These vectors are crucial for gene therapy and gene transfer. The reason that they are so useful is because their genomes are very simple and easy to use. Retroviruses have the ability to integrate into host cell genomes very well, which allows for the long term expression of their genome. One specific gammaretrovirus that is commonly used as a retroviral vector is the Moloney murine leukemia virus. [7] [9]
A specific gammaretrovirus called xenotropic murine leukemia virus-related virus (XMRV) has been found to infect prostate cancer tissue in laboratories. XMRV is a recombinant virus observed incidentally as a result of recombination between two endogenous mouse retroviruses by prostate cancer researchers in the mid-1990s. Although it can infect human tissue, no known disease is associated with the infection [10] [11] [12] and it is unlikely to exist outside laboratories. [13] Alleged discovery of XMRV in blood cells of patients with chronic fatigue syndrome in 2009 caused a controversy and eventual retraction. [13] [14] There were over 50 human cancer cell lines that were claimed to be linked to murine leukemia virus-related virus or murine leukemia virus. There have also been claimed discoveries of murine gammaretroviruses in lung cancer cell lines. While it was unclear what role these viruses have in the cancer development, it was believed that they are most prevalent during the tumor developing stage of the cancer by inhibiting tumor suppressing genes. [8]
Gammaretrovirus is a part of the retroviridae family. Gammaretroviruses are considered zoonotic viruses because they are found in many different mammalian species, such as mice, cats, pigs, primates, cows, and birds. However, bats are the primary reservoir for many gammaretroviruses. Bats can have a prolonged exposure to a variety of pathogens without showing any warning signs, which leads to the debated belief that bats have the ability to develop immunity to viruses that may harm other species. So, it is possible for bats to harbor not only one, but several types of gammaretroviruses. This claim is supported by a sequencing transcriptome profiling technique, and a polymerase chain reaction. Researchers also looked into several different types of bat species to solidify the claim that bats are the main reservoir for gammaretroviruses. The gammaretroviruses can be spread horizontally, animal to animal, or vertically from parent to offspring. [15]
Another gammaretrovirus reservoir was discovered in the genome of the bottlenose dolphin. This gammaretrovirus called Tursiops truncates endogenous retrovirus, was thought to be from extant mammalian endogenous gammaretroviruses. The Tursiops truncates endogenous retrovirus original invasion dates back to approximately 10–19 million years ago, and was identified in killer whale endogenous gammaretrovirus which invaded over 3 million years ago. In 2009, another endogenous gammaretroviruses were detected in a species of killer whale, as well as nine other cetacean genomes. So gammaretrovirus genomes are present in both aquatic and terrestrial mammal species. [16]
Gammaretrovirus is a spherical, enveloped virion ranging from 80–100 nm in diameter. It contains a nucleocapsid, reverse-transcriptase, integrase, capsid, protease, envelope and surface units. The nucleocapsid is a nucleic acid protein assembly within the virus particle, it is a substructure of the virion. Reverse-transcriptase is the enzyme responsible for the transformation of RNA to DNA during the virion replication cycle. Integrase works with reverse transcriptase to convert RNA to DNA. The capsid is a protein shell that surrounds the genome of a virus particle, its main functions are to protect and deliver the genome to the host cell. The viral envelope is the membrane that surround the viral capsid, it is a host cell derived lipid bilayer. [6] [17]
The genome of the gammaretrovirus is a single-stranded RNA (+) genome that is approximately 8.3 kb in size. It has a 5’ cap with a 3’ poly-A tail, and it contains two long terminal repeater regions at both the 5’ and 3’ ends. These long terminal repeat regions have the U5, R, and U3 regions as well as a polypurine tract at the 3’ end and a primer binding site at the 5’ end. The typical gammretrovirus genome contains the gag gene, pol gene, and an env gene. [6]
The gammaretrovirus will act as a parasite to use cellular host factors to deliver genome into a host's cell nucleus, where they will use the cell's machinery to replicate the viral genome and continue the spread throughout the host organism. Because it is a single-stranded RNA(+) with a DNA intermediate genome, it has the ability to copy its viral RNA genome directly into mRNA. Against the central dogma of biology, it also reversely transcribes its RNA genome into DNA. [17]
Virion attach the host cell receptors via the SU glycoprotein, then the TM glycoprotein assists with fusion with the cell membrane. The virus will then begin uncoating, and a linear double-stranded DNA molecule is formed from the single-stranded RNA(+) genome via reverse transcription. The enzyme responsible for reverse transcription is reverse transcriptase. The host nuclear membrane is disassembled during mitosis and the viral double-stranded DNA is able to enter the host nucleus. Viral double-stranded DNA is then integrated into the host cell genome via viral integrase, an enzyme that allows for viral DNA integration into host DNA. The virus is now referred to as a provirus, which means the gammaretrovirus DNA has integrated into the host cell genome and is now the template for the formation of viral mRNA and genomic RNA. Double-stranded DNA is transcribed by Pol II and will produce both spliced and unspliced RNA strands, these spliced RNA strands will leave the host cell nucleus. The unspliced viral RNA translation produces env, gag, and gag-pol polyproteins. The Env becomes a polypeptide precursor and will cleave to produce a receptor binding surface. Next the virion is assembled in the host cell membrane, and the viral RNA genome is packaged. The virions bud from the plasma membrane and release into the host. After virions release from host cells the process is repeated on the next cell the active viral particle comes across. [6] [17]
Gammaretrovirus outbreaks are common in koalas. In fact, they have been linked to Koala Immune Deficiency Syndrome (KIDS), which is similar to human immunodeficiency syndrome. Koala Immune Deficiency Syndrome affects the immune system of various populations of koalas, leaving them more prone to becoming infected with diseases or diagnosed with cancer. Similar to HIV, Koala Immune Deficiency Syndrome can be passed on to offspring as well as be transmitted to other koalas or species on animals. The virus is common in captive koalas. In fact, in a population of captive koalas in Queensland 80% of the deaths are connected with gammaretroviruses. This colony is on high alert that their populations of koalas could be extinct in the near future, researchers are concerned that an epidemic may break out in Queensland. [18] [19]
Vaccines have been discovered and provided for various gammaretroviruses. Namibia hosts the largest population of wild cheetahs in the world, making it a vital population for understanding the biology and natural behaviour of this species. In June 2002, researchers began testing animals for the presence of feline leukemia virus, since the concern arose that viral infection could cause a major health problem in Namibia's cheetah population. Through this testing, antibodies were collected to develop a feline leukemia virus vaccine. This vaccine has proven to be successful in the Namibian cheetahs, as 86% of the vaccinated cheetahs tested positive for the feline leukemia virus antibodies. With such a high vaccinated percentage, the cheetahs are in a condition where there's more than enough of the population that is vaccinated to prevent an outbreak of a gammaretrovius such as feline leukemia virus. [20]
Along with vaccinations, host restriction of gammaretroviruses and other types of retroviruses are common among animals. Many hosts have a gene that blocks the replication cycle of retroviruses, including gammaretrovirus. This gene was discovered using a non-virulent protein of murine leukemia virus. This protein will block replication of some murine leukemia virus strains following reverse transcription. The restriction of the virus depends on the interaction of the protein and the invading virus.[ citation needed ]
A provirus is a virus genome that is integrated into the DNA of a host cell. In the case of bacterial viruses (bacteriophages), proviruses are often referred to as prophages. However, proviruses are distinctly different from prophages and these terms should not be used interchangeably. Unlike prophages, proviruses do not excise themselves from the host genome when the host cell is stressed.
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 (backward). 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.
Hepadnaviridae is a family of viruses. Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera. Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas, and cirrhosis. It is the sole accepted family in the order Blubervirales.
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.
An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term oncornaviruses was used to denote their RNA virus origin. With the letters RNA removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with tumor virus or cancer virus. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.
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.
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 murine leukemia viruses 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.
Pseudodiploid or pseudoploid refers to one of the essential components in viral reproduction. It means having two RNA genomes per virion but giving rise to only one DNA copy in infected cells.
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.
The gag-onc fusion protein is a general term for a fusion protein formed from a group-specific antigen ('gag') gene and that of an oncogene ('onc'), a gene that plays a role in the development of a cancer. The name is also written as Gag-v-Onc, with "v" indicating that the Onc sequence resides in a viral genome. Onc is a generic placeholder for a given specific oncogene, such as C-jun..
Xenotropic murine leukemia virus–related virus (XMRV) is a retrovirus which was first described in 2006 as an apparently novel human pathogen found in tissue samples from men with prostate cancer. Initial reports erroneously linked the virus to prostate cancer and later to chronic fatigue syndrome (CFS), leading to considerable interest in the scientific and patient communities, investigation of XMRV as a potential cause of multiple medical conditions, and public-health concerns about the safety of the donated blood supply.
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.
Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses and those that use naked DNA or DNA complexes.
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.
Lentiviral vectors in gene therapy is a method by which genes can be inserted, modified, or deleted in organisms using lentiviruses.
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.
Riboviria is a realm of viruses that includes all viruses that use a homologous RNA-dependent polymerase for replication. It includes RNA viruses that encode an RNA-dependent RNA polymerase, as well as reverse-transcribing viruses that encode an RNA-dependent DNA polymerase. RNA-dependent RNA polymerase (RdRp), also called RNA replicase, produces RNA from RNA. RNA-dependent DNA polymerase (RdDp), also called reverse transcriptase (RT), produces DNA from RNA. These enzymes are essential for replicating the viral genome and transcribing viral genes into messenger RNA (mRNA) for translation of viral proteins.
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.
