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.

Introduction

Many endogenous retroviruses, closely related to exogenous gammaretroviruses, are present in the DNA of mammals (including humans), birds, reptiles and amphibians. Many also share a conserved RNA structural element called a core encapsidation signal.

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.

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.

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.

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.

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 and it is unlikely to exist outside laboratories. Alleged discovery of XMRV in blood cells of patients with chronic fatigue syndrome in 2009 caused a controversy and eventual retraction. 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.

  • Gammaretrovirus aviretend, Reticuloendotheliosis virus
  • Gammaretrovirus avisplnec, Trager duck spleen necrosis virus
  • Gammaretrovirus chisyn, Chick syncytial virus
  • Gammaretrovirus felleu, Feline leukemia virus
  • Gammaretrovirus fibijimursar, Finkel-Biskis-Jinkins murine sarcoma virus
  • Gammaretrovirus gibleu, Gibbon ape leukemia virus
  • Gammaretrovirus Hamursar, Harvey murine sarcoma virus
  • Gammaretrovirus hazufelsar, Hardy-Zuckerman feline sarcoma virus
  • Gammaretrovirus Kimursar, Kirsten murine sarcoma virus
  • Gammaretrovirus koa, Koala retrovirus
  • Gammaretrovirus momursar, Moloney murine sarcoma virus
  • Gammaretrovirus murleu, Moloney murine leukemia virus
  • Gammaretrovirus porConc, Porcine type-C oncovirus
  • Gammaretrovirus snythefelsar, Snyder-Theilen feline sarcoma virus
  • Gammaretrovirus woomonsar, Woolly monkey sarcoma virus

Hosts and reservoirs

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.

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.

Structure

thumb|upright=1.5|Schematic Drawing: immature and mature [[virion of Gammaretrovirus

Genome

[[File:Gammaretrovirus genome.png|thumb|upright=1.5|Gammaretrovirus genome map

KoRV belongs to the gammaretrovirus genus and is closely related to GaLV with an 80% nucleotide similarity. The retrovirus is isolated from lymphomas and leukemias, present within infected captive and free-living koala populations in Australasia. Accordingly, a study published within the journal of virology, Molecular Dynamics and Mode of Transmission of Koala Retrovirus as It Invades and Spreads through a Wild Queensland Koala Population, highlights that 80% of koalas that developed neoplasia was also KoRV-B positive, thereby linking the widespread infection of leukemia and lymphoma to KoRV. At present, KoRV is the only retroviral that induces germ-line infections and therefore presents the opportunity for scientists to understand the processes regulating retrovirus endogenization.

9 subtypes of KoRV have been identified, with the primary strains being; KoRV-A, KoRV-B and KoRV-J, which induces immodulation resulting in neoplastic syndromes and chlamydiosis. Moreover, the study demonstrated the diseases associated with KoRV-B including; developed abdominal lymphoma, a nonspecified proliferative/bone marrow condition, osteochondroma and mesothelioma. Nature by Tarlington and colleagues, provides epidemiological evidence that germline infections are present in populations found in Queensland, yet some individuals in Southern Australia lack the provirus, suggesting that retroviral endogenization began in Northern Australia between the last 100 to 200 years. First discovered in 1964 within a cluster of cats with lymphosarcoma. FeLV is identified as the infectious agent causing immunomodulation within bone marrow and the immune system, which renders infected cats susceptible to a variety of secondary and opportunistic infections. Associated diseases of FeLV include; lymphoma, non-regenerative anemias and thymic degenerative disease. Currently, the prevalence of FeLV has decreased since the 1970s and 1980s, due to veterinary interventions, vaccination, biosecurity protocols and quarantine or euthanasia of infected animals. Accurate blood testing procedures revolving around the detection of FeLV P27 enables diagnosis via two methods; enzyme-linked immunosorbent assay (ELISA), which detects the presence of free FeLV particles that are found in the bloodstream and indirect immunofluorescent antibody assay (IFA), which detects the presence of retroviral particles within white blood cells.

FeLV is horizontally and vertically transmitted through biomaterials; saliva, blood, breast milk, urine and feces. Furthermore, transmission can also occur postnatally or prenatally within parent-progeny relationships. The potency of parasitic fleas as a viral vector for FeLV was identified in 2003, which confirmed horizontal transmission of FeLV without close contact with infected individuals. Furthermore, the three strains of FeLV are A,B,C. FeLV-A is the least pathogenic strain that is transmittable in nature especially within unvaccinated animals. Contrarily, FeLV-B is derived via recombination of exogenous FeLV-A with endogenous sequences (enFeLV) whilst the limited research into the origins of FeLV-C leans towards recombination/ or mutation.

Porcine endogenous retrovirus (PERV)

PERV was first described in 1970, belonging to the gammaretrovirus genus, Orthoretrovirinae subfamily and Retroviridae family,. PERV is categorised into three replication competent subtypes: PERV-A, PERV-B and PERV-C. PERV-A and PERV-B are polytropic viruses which are capable of infecting humans and porcine cells, whereas PERV-C is an ecotropic virus which effects only porcine cells. The cross-species transmission of PERV's in human cells have been demonstrated in vitro which raises concern regarding the xenotransplantation of porcine cells, tissues and organs.

References

  • Viralzone: Gammaretrovirus