Equine foamy virus

Last updated
Equine foamy virus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Equispumavirus
Species:
Equine foamy virus

Equine foamy virus (EFV), also called foamy virus (FV), is virus in the genus Equispumavirus. [1] It shares similarities, with respect to replication, with lentiviruses. EFV, along with other FVs are from the family Retroviridae and subfamily Spumaretrovirinae. Spumarivuses, such as EFV, are complicated retroviruses that have been characterized in many animals including nonhuman primates, cattle, cats. Additionally, these viruses have been identified in animals that most often carry lentiviruses. [1]

Contents

The name foamy virus can be attributed to the foamy appearance of the cells upon rapid lysation and syncytium formation, vacuolization and cellular death, which is also known as a cytopathic effect (CPE). [1]

EFV has been found to display a similar capsid structure along with exhibiting similar functionality to other foamy viruses, yet differs in some respects. [2]

Viral classification

Equine foamy virus is a single-stranded RNA-RT virus. It is classified in the genus Equispumavirus, subfamily Spumaretrovirinae and family Retroviridae . Foamy viruses are the only viruses of the Retroviridae that reside in the subfamily Spumaretrovirinae. The remainder of the viruses from the family Retroviridae are classified under the subfamily Orthoretrovirinae , which include alpharetroviruses, betaretroviruses, gammaretroviruses, deltaretroviruses, epsilonretroviruses and lentiviruses. The separation of foamy viruses under a different subfamily was determined in 2002 by the International Committee on Taxonomy of Viruses (ICTV) based on a difference in replication pathways, thus making a clear distinctive quality of foamy viruses from other Retroviridae. [3]

EFV has characteristics of viruses from other genera in Spumaretrovirinae. EFV is similar to viruses from the paraetrovirus genus because of their formations of a pol mRNA and their infectivity of viral DNA. [2] Although not fully researched, EFV has been found to share several distinct qualities with lentiviruses including transmission, natural hosts, and replication [2] [4]

Identification

Foamy viruses were first discovered and described in 1954 in kidney cultures of simians and were first isolated in 1955. [5] [6] From then on, a variety of foamy viruses were isolated from several species including cats, cows, monkeys, humans. [5] With the discovery and isolation of foamy viruses in other natural hosts such as bovine, feline, and simian, the hypothesis that an equine foamy virus might exist was explored in the late 1900s to early 2000s [1] [5]

Blood samples of naturally infected horses were taken to determine the existence of an equine foamy virus. Because foamy viruses have been linked to lifelong yet not pathogenic diseases, the presence of antibodies without the presence of a disease or illness is a key indicator of a foamy virus infection. [1] Since antibodies against foamy viruses are not often found in animals three to five months of age due to passive immunity, the blood samples were only taken from sexually mature horses and horses who had surpassed the range of passive immunity and were in close living quarters with horses that had the virus [1] [2]

Genome

Through nucleotide sequence analyses and molecular cloning, EFV was compared to other foamy viruses regarding the organization of their genome along with the ultrastructure. [2] While the overall organization of EFV is similar to other foamy viruses, it was found to share minor similarities to primate foamy viruses. EFV is most similar sequentially to bovine foamy virus (BFV), yet it still only shares 40% of its sequence with it [2]

Size

Equine foamy virus, like other foamy viruses, has been reported to have a rather large genome. [2] Foamy virus genomes can range anywhere from 12 to 30 kb in length. [1] The genome length of EFV specifically has not been recorded [2]

Genes and proteins

Within this genome, classical structural genes common to FVs are present such as gag, env, and pol. [7] Sequence analysis has also led to the discovery that while EFV shares most of the same features as other foamy viruses, it differs slightly with respect to the noncoding regions, the gag gene, the pol gene, the env gene and the regulatory region [7]

In addition to the encoded retroviral genes pol, gag and env, the genome of EFV also encodes for two more genes: tas and bet. [2] Both of the two additional genes, although bet has been under researched, play a strong role in replication. [2] One of EFVs two promoters is transactivated by the protein made from tas, therefore, tas is required for replication of the entire genome to occur [2]

The auxiliary protein Tas is located downstream of the env gene and is encoded by ORF1. [8] Tas, which is a specific feature of foamy viruses, binds directly and specifically to viral DNA on both the LTR (long terminal repeat) and the IP (internal promoter). Proteins such as Gag, Env, Pol, Tas and Bet are a result of the synthesis of mRNAs at the 5′ LTR, while IP results in the expression of other auxiliary proteins. [9] The two aforementioned promoters were found to rely directly on the presence of Tas [8]

The location of Gag was also determined to be different from the location in other foamy viruses. [9] In EFV, Gag was found to be located in the nucleus and the cytoplasm and Env was found to reside in the Golgi complex instead of the endoplasmic reticulum (ER). [2] [9] Additionally, while short intra-cytoplasmic Env tails were found in other foamy viruses, the tail was completely absent in EFV [9]

Structure

The appearance of EFV is similar to other foamy viruses in the sense that they are approximately 100 nm in diameter, spiked with glycoproteins and are enveloped particles with a clear core. [1] [10] [2]

Genome replication cycle

Retrovirus and the Use of Reverse Transcriptase

The infectious particles of EFV have DNA not RNA due to the matter that reverse transcription occurs later in the replication cycle. [1] Because EFV is a retrovirus, the enzyme reverse transcriptase is used to form a dsDNA intermediate from the positive and linear ssRNA. The resulting DNA spans the length of the entire genome and is organized in a linear manner. [1]

Budding

EFV is unique from other foamy viruses as the region of viral budding does not occur from the ER, but rather it buds solely from the plasma membrane. [10] [7] [11] This is due to the fact that the glycoprotein envelope on EFV lacks a dilysine retrieval motif that is commonly found in the C terminus of other foamy viruses, specifically primate foamy viruses. [10] [2]

Promoters

EFV has two initiation sites for the synthesis of (+)DNA: the 3’ LTR polypurine tract (PPT) and at the 3’ end of the PPT site located within pol. [7] Gapped linear DNA duplex intermediates are the result of this dual initiation of EFV. [7] While replication is similar to lentiviruses with regards to the aforementioned promoter regions, it is also similar to the hepadnaviridae cycle. The EFV transactivator protein, Tas, binds to one of the promoter regions to promote the expression of specific genes. Unlike all other FVs, the Tas protein is not localized specifically to the nucleus. Instead, the transactivator gene for EFV was found both in the nucleus and in the cytoplasm, which is a characteristic unique to lentiviruses. [11]

It has also been found that upon persistent infection with EFV, the viral genome replication system becomes defective. [11]

Pathogenesis and transmission

Like other foamy viruses, infection with equine foamy virus is lifelong, yet the natural hosts do not display any pathological characteristics and are rather asymptomatic. [12] In vitro EFV has been found to form large vacuoles in the cells, while such vacuoles are absent in vivo. [1]

Current research may suggest that equine foamy virus serves as a cofactor in the contraction of equine lentivirus infection. The exact link between the two has yet to be researched enough to conclude causative relations. [2]

While the mechanism of transmission is not well understood and under researched, exchange of bodily fluids with an infected animal seems to be the most probable means of transmission. [1] [4] Through studies performed with simian foamy virus, it can be predicted that EFV can spread through saliva and bites, yet there is no evidence to suggest that any foamy virus can be sexually transmitted. [1] [4] While rare, EFV is capable of infecting humans during a zoonotic event. Although no cases have been reported to date, only those in extremely close contract with a persistently infected horse would be at risk for contracting the virus. [4] [1]

Tropism

EFV has a broad cell tropism which allows it to infect a variety of species including, but not limited to, hamsters, rabbits, and simians. [1]

The magnitude of the infection can vary widely depending on the type of cell infected. While most infected cells display the foamy appearance unique to foamy viruses, it has been found that certain fibroblast cell lines are more sensitive to the cytopathic effects (CPE). [1]

Some cell lines are more prone to chronic infection than others, while some cell lines have been found to be unaffected by foamy viruses in general. [1] Transformed lines such as those originating from myeloid, erythroid and lymphoid cells have been known to be extremely sensitive to the CPE of EFV while monocytes are notorious for being unresponsive to the CPE in other foamy viruses, and thus it is predicted that cells infected with EFV will respond similarly. [1]

Future implications

Since EFV is nonpathogenic, has a wide cellular tropism and buds from the plasma membrane, it may be a better vector for gene therapy than other foamy viruses. [1] [13] [14] The budding characteristic of EFV from the plasma membrane would result in higher viral titers along with an intact cellular membrane. [11] Additionally, because EFV has two promoters, insertional mutagenesis would be safe and more accurate than other retroviruses with only one promoter. [2]

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.

<i>Simian immunodeficiency virus</i> Species of retrovirus

Simian immunodeficiency virus (SIV) is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island, which was isolated from the mainland by rising sea levels about 11,000 years ago, it has been concluded that SIV has been present in monkeys and apes for at least 32,000 years, and probably much longer.

SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that sometimes causes tumors in animals, but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic DNA replication and transcription.

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.

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.

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.

Human foamy virus (HFV) is a retrovirus and specifically belongs to the genus Spumavirus. The spumaviruses are complex and significantly different from the other six genera of retroviruses in several ways. The foamy viruses derive their name from the characteristic ‘foamy’ appearance of the cytopathic effect (CPE) induced in the cells. Foamy virus in humans occurs only as a result of zoonotic infection.

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.

A helper dependent virus, also termed a gutless virus, is a synthetic viral vector dependent on the assistance of a helper virus in order to replicate, and can be used for purposes such as gene therapy. Naturally-occurring satellite viruses are also helper virus dependent, and can sometimes be modified to become viral vectors.

Visna-maedi virus from the genus Lentivirus and subfamily Orthoretrovirinae, is a retrovirus that causes encephalitis and chronic pneumonitis in sheep. It is known as visna when found in the brain, and maedi when infecting the lungs. Lifelong, persistent infections in sheep occur in the lungs, lymph nodes, spleen, joints, central nervous system, and mammary glands; The condition is sometimes known as ovine progressive pneumonia (OPP), particularly in the United States, or Montana sheep disease. White blood cells of the monocyte/macrophage lineage are the main target of the virus.

Bovine immunodeficiency virus (BIV) is a retrovirus belonging to the genus Lentivirus. It is similar to the human immunodeficiency virus (HIV) and infects cattle. The cells primarily infected are lymphocytes and monocytes/macrophages.

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.

<span class="mw-page-title-main">Lentiviral vector in gene therapy</span>

Lentiviral vectors in gene therapy is a method by which genes can be inserted, modified, or deleted in organisms using lentiviruses.

Human Endogenous Retrovirus-W (HERV-W) is the coding for a protein that would normally be part of the envelope of one family of Human Endogenous Retro-Viruses, or HERVs.

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.

<span class="mw-page-title-main">Enzootic nasal tumor virus</span> Species of virus

The enzootic nasal tumor virus of the betaretrovirus genus is a carcinogenic retrovirus that causes enzootic nasal adenocarcinoma in sheep and goats. Strain ENTV-1 is found in sheep and strain ENTV-2 is found in goats. The virus causes tumor growth in the upper nasal cavity and is closely related to JSRV which also causes respiratory tumors in ovine. The disease, enzootic nasal adenocarcinoma is common in North America and is found in sheep and goats on every continent except New Zealand and Australia. There are more than 27 betaretroviruses similar to ENVT and JSRV in the ovine genome. In the future, research on ENTV may become important in studying viruses that cause human lung cancer.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Meiering CD, Linial ML (January 2001). "Historical perspective of foamy virus epidemiology and infection". Clinical Microbiology Reviews. 14 (1): 165–176. doi:10.1128/CMR.14.1.165-176.2001. PMC   88968 . PMID   11148008.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Tobaly-Tapiero J, Bittoun P, Neves M, Guillemin MC, Lecellier CH, Puvion-Dutilleul F, et al. (May 2000). "Isolation and characterization of an equine foamy virus". Journal of Virology. 74 (9): 4064–4073. doi:10.1128/jvi.74.9.4064-4073.2000. PMC   111920 . PMID   10756018.
  3. ↑ Saïb A (2003). "Non-primate Foamy Viruses". Foamy Viruses. Current Topics in Microbiology and Immunology. Vol. 277. Springer, Berlin, Heidelberg. pp. 197–211. doi:10.1007/978-3-642-55701-9_9. ISBN   9783642629341. PMID   12908774.
  4. 1 2 3 4 Heneine W, Schweizer M, Sandstrom P, Folks T (2003). "Human infection with foamy viruses". Current Topics in Microbiology and Immunology. 277: 181–196. doi:10.1007/978-3-642-55701-9_8. ISBN   978-3-642-62934-1. PMID   12908773.
  5. 1 2 3 Tyrrell D, Gard S (2013-12-19). The Simian Viruses / Rhinoviruses. Springer. ISBN   9783662394472.
  6. ↑ Sakai K, Ami Y, Suzaki Y, Matano T (December 2016). "First Complete Genome Sequence of a Simian Foamy Virus Isolate from a Cynomolgus Macaque". Genome Announcements. 4 (6): e01332–16. doi:10.1128/genomeA.01332-16. PMC   5137406 . PMID   27908992.
  7. 1 2 3 4 5 Saïb A (2003). "Non-primate Foamy Viruses". Foamy Viruses. Current Topics in Microbiology and Immunology. Vol. 277. Berlin, Heidelberg: Springer. pp. 197–211. doi:10.1007/978-3-642-55701-9_9. ISBN   9783642629341. PMID   12908774.
  8. 1 2 Lecellier CH, Vermeulen W, Bachelerie F, Giron ML, Saïb A (April 2002). "Intra- and intercellular trafficking of the foamy virus auxiliary bet protein". Journal of Virology. 76 (7): 3388–3394. doi:10.1128/JVI.76.7.3388-3394.2002. PMC   136056 . PMID   11884565.
  9. 1 2 3 4 Flügel RM, Pfrepper KI (2003). "Proteolytic processing of foamy virus Gag and Pol proteins". Current Topics in Microbiology and Immunology. 277. Springer, Berlin, Heidelberg: 63–88. doi:10.1007/978-3-642-55701-9_3. ISBN   9783642629341. PMID   12908768.{{cite journal}}: Cite journal requires |journal= (help)
  10. 1 2 3 Shaw KL, Lindemann D, Mulligan MJ, Goepfert PA (February 2003). "Foamy virus envelope glycoprotein is sufficient for particle budding and release". Journal of Virology. 77 (4): 2338–2348. doi:10.1128/JVI.77.4.2338-2348.2003. PMC   141096 . PMID   12551971.
  11. 1 2 3 4 Lecellier CH, Neves M, Giron ML, Tobaly-Tapiero J, Saïb A (July 2002). "Further characterization of equine foamy virus reveals unusual features among the foamy viruses". Journal of Virology. 76 (14): 7220–7227. doi:10.1128/JVI.76.14.7220-7227.2002. PMC   136322 . PMID   12072521.
  12. ↑ "Simiispumavirus". viralzone.expasy.org. Retrieved 2017-11-03.
  13. ↑ Trobridge GD (November 2009). "Foamy virus vectors for gene transfer". Expert Opinion on Biological Therapy. 9 (11): 1427–1436. doi:10.1517/14712590903246388. PMC   2782412 . PMID   19743892.
  14. ↑ Mergia A, Heinkelein M (2003). "Foamy virus vectors". Current Topics in Microbiology and Immunology. 277: 131–159. doi:10.1007/978-3-642-55701-9_6. ISBN   978-3-642-62934-1. PMID   12908771.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.