Simian foamy virus (SFV), historically human foamy virus (HFV), is a species of the genus Simiispumavirus 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. 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.
Description Although the simian foamy virus is endemic in African apes and monkeys, there are extremely high infection rates in captivity, ranging from 70% to 100% in adult animals. As humans are in close proximity to infected individuals, people who have had contact with primates can become infected with SFV, making SFV a zoonotic virus. Its ability to cross over to humans was proven in 2004 by a joint United States and Cameroonian team which found the retrovirus in gorillas, mandrills, and guenons; unexpectedly, they also found it in 10 of 1,100 local Cameroon residents. Of those found infected, the majority are males who had been bitten by a primate. While this only accounts for 1% of the population, this detail alarms some who fear the outbreak of another zoonotic epidemic. SFV causes cells to fuse with each other to form syncytia, whereby the cell becomes multi-nucleated and many vacuoles form, giving it a "foamy" appearance.
Structure The SFV is a spherical, enveloped virus that ranges from 80 to 100 nm in diameter. The cellular receptors have not been characterized, but it is hypothesized that it has a molecular structure with near ubiquitous prevalence, since a wide range of cells are permissible to infection. FV is characterized by an immature looking core with an electron lucent center with glycoprotein spikes on the surface. As a retrovirus, SFV poses the following structural characteristics:
Envelope: Composed of phospholipids taken from a lipid bilayer, in this case the endoplasmic reticulum; this difference gives FV a unique morphology. Additional glycoproteins are synthesized from the env gene. The envelope protects the interior of the virus from the environment, and enables entry by fusing to the membrane of the permissive cell. RNA: The genetic material that carries the code for protein production to create additional viral particles. Proteins: consisting of gag proteins, protease (PR), pol proteins, and env proteins. Group-specific antigen (gag) proteins are major components of the viral capsid. Protease performs proteolytic cleavages during virion maturation to make mature gag and pol proteins. Pol proteins are responsible for synthesis of viral DNA and integration into host DNA after infection. Env proteins are required for the entry of virions into the host cell. The ability of the retrovirus to bind to its target host cell using specific cell-surface receptors is given by the surface component (SU) of the Env protein, while the ability of the retrovirus to enter the cell via membrane fusion is imparted by the membrane-anchored trans-membrane component (TM). Lack of or imperfections in Env proteins make the virus non-infectious.
Genome As a retrovirus, the genomic material is monopartite, linear, positive-sense single-stranded RNA that forms a double stranded DNA intermediate through the use of the enzyme reverse transcriptase. The RNA strand is approximately 12kb's in length, with a 5'-cap and a 3'poly-A tail. The first full genome annotation of a proviral SFV isolated from cynomolgus macaque (Macaca fascicularis) had been performed in December 2016, where it revealed two regulatory sequences, tas and bet, in addition to the structural sequences of gag, pol and env. There are two long terminal repeats (LTRs) of about 600 nucleotides long at the 5' and 3' ends that function as promoters, with an additional internal promoter (IP) located near the 3' end of env. The LTRs contain the U3, R, and U5 regions that are characteristic of retroviruses. There is also a primer binding site (PBS) at the 5'end and a polypurine tract (PPT) at the 3'end. Whereas gag, pol, and env are conserved throughout retroviruses, the tas gene is unique and found only in spumaviruses. It encodes for a trans-activator protein required for transcription from both the LTR promoter and the IP. The synthesized Tas protein, which was initially known as Bel-1, is a 36-kDa phosphoprotein which contains an acidic transcription activation domain at its C-terminus and a centrally located DNA binding domain. The Bet protein is required for viral replication, as it counteracts the innate antiretroviral activity of APOBEC3 family defense factors by obstructing their incorporation into virions. The DNA found is linear and the length of the genome. The genome encodes the usual retroviral genes pol, gag, and env as well as two additional genes tas or bel-1 and bet. The role for bet is not quite clear, research has shown that it is dispensable for replication of the virus in tissue culture. Recently, a novel mechanism was reported where foamy virus accessory protein Bet (unlike HIV-1 Vif) impaired the cytoplasmic solubility of APOBEC3G. The tas gene, however, is required for replication. It encodes a protein that functions in transactivating the long terminal repeat (LTR) promoter. FV has a second promoter, the internal promoter (IP) which is located in the env gene. The IP drives expression of the tas and bet genes. The IP is also unique in that the virus has the capacity to transcribe mRNAs from it; usually the complex retroviruses exclusively express transcripts from the LTR. The structural genes of FV are another one of its unique features. The Gag protein is not efficiently cleaved into the mature virus which lends to the immature morphology. The Pol precursor protein is only partially cleaved; the integrase domain is removed by viral protease. As in other retroviruses, the Env protein is cleaved into surface and transmembrane domains but the FV Env protein also contains an endoplasmic reticulum retention signal which is part of why the virus buds from the endoplasmic reticulum. Another area of difference between FV and other retroviruses is the possibility of recycling the core once the virus is in the cell.
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