Spumaviruses
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Spumaviruses , better known as foamy viruses (FV), officially Spumaretrovirinae are enveloped single (+) - strand - RNA viruses (ss (+) RNA) from the family of retroviruses . They are widespread in various species of monkey (SFV), cats ( FFV ), cattle (BFV) and horses ( EFV ) and can rarely infect humans. Neither the natural hosts nor humans are known to have a disease pattern caused by foamy viruses. Due to the peculiarities of their replication cycle and their molecular biology , some of which have analogies to hepadnaviruses , they form their own subfamily within the retroviruses as Spumaretrovirinae , which are differentiated from the other retroviruses in the subfamily of Orthoretrovirinae . The scientific interest in foamy viruses relates in particular to their special position between hepadna and orthoretroviruses and to their possible use as viral vectors in the context of gene therapy.
Foamy viruses as special retro viruses
Foamy viruses are the only type of retrovirus for which no associated disease has yet been described. The reason for this is ultimately unknown. However, comparisons of foamy viruses from different species of apes have shown that the respective foamy viruses and their hosts probably developed together over many, up to 30 or 40 million years. This would make them the oldest known vertebrate RNA viruses. This coevolution could be a reason for the apathogenicity of the foamy viruses, since the virus and host were able to optimally adapt to one another over the course of time.
Foamy viruses lead to a persistent infection with low replication rates in their hosts . There are indications that replication takes place mainly in the oral mucosa or the salivary glands and that transmission between the animals occurs mainly through biting. It is still largely unknown why foamy viruses lead to a non-pathogenic persistent or latent infection in vivo , although they show a pronounced cytopathic effect (CPE) in cell culture . This CPE shows a characteristic foamy appearance of the cell culture with confluent, multinuclear and vacuolating giant cells and also led to the naming of these viruses (English foamy foamy, Latin spuma foam)
The demarcation of the foamy viruses as the only genus of the subfamily Spumaretrovirinae compared to the other six retroviral genera in the subfamily of the Orthoretrovirinae occurs, in addition to some other peculiarities in their molecular biology, mainly due to the fact that the reverse transcription takes place at a later point in time in the replication cycle, i.e. before the virus particle leaves the cell, and thus DNA is present in the virions as functional genetic material and not RNA as in all other retroviruses.
history
The first descriptions of the typical foamyviral "foamy" CPE in a cell culture from monkey tissue and the isolation of the causative, cell-free transferable agent date from the years 1954/55. In the time that followed, it was possible to isolate similar foamy viral agents from different species of monkeys, which were differentiated on the basis of serological properties and were initially numbered in the order in which they were discovered (SFV-1 from macaques 1955 to SFV-11 from orangutans 1994) . The foamy viruses were later named after the species of monkey they came from, e.g. B. subsequently SFVmac for SFV-1 and SFVora for SFV-11.
Foamy viruses were isolated from cats and cattle independently of one another in 1969, and from horses in 1999. Unconfirmed individual reports on the occurrence of foamy viruses are also available in some other mammals such as California sea lions and hamsters.
In 1971, a foamy virus was isolated from a cell culture obtained from a Kenyan patient with nasopharyngeal carcinoma . Since HTLV and HIV were not discovered until 1980 and 1983, respectively, this "human" foamy virus (HFV) was the first retrovirus to be isolated from human tissue. A serological similarity between HFV and the SFV-6 isolate known from chimpanzees was soon established, which is why the question arose shortly after the discovery whether HFV was a real human retrovirus or whether a person was infected with one Chimpanzee virus. This question was resolved two decades later, when new methods such as sequencing became widespread, and it has been widely believed since 1994/95 that HFV is not a human retrovirus in the strict sense of the word as HTLV or HIV but rather a contamination of the original cell culture or a cross-species infection of the Kenyan patient with an SFVcpz found in chimpanzees. The latter is supported by the fact that the patient came from an area where chimpanzees are common. To make it clear that "HFV" is not actually a human foamy virus, it has since been referred to as SFVcpz (hu), or, since much of the research on foamy viruses has been carried out on this isolate, also as prototype foamy virus (PFV) .
With the isolation of PFV from human tissue, the search for a disease caused by this putative human retrovirus began. The origin of a nasopharyngeal carcinoma and the relationship of the foamy viruses to the oncoviruses initially suggested a possible tumor association. However, individual positive reports could never be confirmed. Research in this regard was pushed again with the discovery of the retroviruses HTLV and HIV, which are pathogenic to humans, in 1980/83, with the search increasingly also referring to autoimmune diseases such as Graves' disease or multiple sclerosis and the like. The respective findings obtained in small patient groups could never be confirmed in larger patient groups. In these smaller studies, mostly only one, often relatively unspecific search method was used, such as B. a Western blot or a PCR . In the subsequent investigations, the specificity was increased by the simultaneous use of several such methods, whereby the results were negative in each case.
Molecular biological studies of the foamy virus genome, the proteins encoded therein and their functions began to a greater extent at the end of the 1980s and continue to this day. The first considerations and experiments on the use of foamy viruses in gene therapy date from the mid-1990s.
Spread in humans and animals
Foamy viruses have been found in both New World monkeys in America and especially in Old World monkeys in Africa and Asia, including the great apes. So now number some of spider monkeys , vervet monkeys , macaques , mandrills , baboons , chimpanzees , gorillas and orangutans foamy viruses have been isolated and partially investigated. In the case of animals kept in captivity, the rate of infected animals reaches values of over 90%. Even in the wild, however, values over 50% are sometimes found. Newborns seem to get antibodies, but not the virus, from the mother. The virus infection occurs rather vertically probably as contact infection during adolescence or young adulthood. It has not yet been definitively clarified whether this happens mainly through bites or possibly also through sexual intercourse.
FFV in cats and BFV in cattle are also quite widespread, but no meaningful figures are yet available about the equine foamy virus, which was only recently discovered in horses. Overall, it is noticeable that the spread of foamy viruses and the spread of lentiviruses show a great deal of similarity, although the reasons for this are still unknown.
Although a human foamy virus in all likelihood does not exist, contrary to previous belief, there are still a number of people infected with foamy viruses. However, these are infections with isolates that come from non-human primates and for which humans are probably a kind of false host. For example, it was not possible to detect a transmission from people who had been infected with SFV for years to their respective partners. Certain risk groups are affected, such as laboratory staff and zookeepers who are in close contact with monkeys and who could possibly be bitten, and especially in certain areas of Africa people who hunt monkeys or handle their carcasses. Transmissions from monkeys as diverse as macaques, baboons and chimpanzees were observed, and the rate of infected people in the risk groups reached around 2-3%. This means that the probability of SFV being transmitted to humans is higher than that of SIV .
In contrast to the orthoretroviruses, which include the and lentiviruses , foamy viruses do not trigger known diseases in the natural main host , reservoir host , or in other hosts after crossing species boundaries.
Molecular biology
The foamy viruses differ in many aspects of their molecular biology and their replication cycle from the orthoretroviruses and have some similarities with the hepadnaviruses , which is why they are also seen as the link between (ortho-) retroviruses and hepadnaviruses. So they do not split Gag into the components known in orthoretroviruses (matrix, capsid, nucleocapsid), but only a short peptide is split off at the C-terminus. Also, Pol is only cleaved once, between RT / RN and IN, while the protease remains connected to the RT. Env also has some special features, such as the presence of a long leader peptide as an integral part of the virion. Most noticeable, however, is the fact that reverse transcription takes place at a later point in time in the replication cycle and the associated presence of DNA in the virion.
Foamy viruses have a complex genome and code for Gag, Pol and Env as well as other proteins, namely Tas (Bel1) and Bet. These are expressed via an internal promoter located in the 3 'region of the Env gene. Tas is the transcriptional transactivator of the spumaviruses and regulates the activity of both promoters. Bet is a functionally homologous protein to HIV-Vif that suppresses cellular immunity factors such as APOBEC-3G / F.
Foamy viruses as viral vectors
Despite their pathological insignificance, they are interesting subjects of study for virus researchers, since one can draw numerous conclusions about the other, pathogenic retroviruses from their structure and the manner in which they multiply. In recent years, foamy viruses have gained great importance in gene therapy studies because they are non-pathogenic and can package a large genome (approx. 14,000 nucleotides ).
Systematics
The International Committee on Taxonomy of Viruses (ICTV) has classified the spumaviruses as a subfamily Spumavirinae (as of November 2018). The genera are:
- Genus Bovispumavirus
- Genus Equispumavirus (with species Equines Foamyvirus )
- Genus Felispumavirus
- Genus Prosimiispumavirus
- Genus Simiispumavirus
Web links
Individual evidence
- ↑ a b c d ICTV: ICTV Taxonomy history: Commelina yellow mottle virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
- ↑ ICTV : Master Species List 2018a v1 MSL including all taxa updates since the 2017 release. Fall 2018 (MSL # 33)
- ↑ SIB: Simiispumavirus , on: ViralZone