Viruses in the subfamily are distinguished by multiple morphological and molecular features (Rethwilm 2010, Hütter et al., 2013, Rethwilm and Lindemann 2013). Virions exhibit a distinctive morphology with prominent surface spikes of approximately 15 nm and a central, uncondensed core. Enveloped virions of approximately 110 nm diameter encompass a core of approximately 60 nm in diameter. Capsid assembly occurs in the cytoplasm prior to budding into intracellular compartments (e.g. Golgi) or from the plasma membrane. Capsid budding requires the presence of Env protein. Unlike orthoretroviruses, no cleavage of Gag protein precursors into matrix protein (MA), capsid protein (CA), and nucleocapsid protein (NC) subunits is detectable in infectious virions, and the otherwise conserved myristylation, major homology region (MHR), and cysteine-histidine (CH) box motifs are not found in spumavirus Gag derived proteins. The Gag protein is cleaved once near the carboxyl-terminus, and the uncleaved and cleaved proteins are both present in virions resulting in a characteristic doublet in protein gels/blots. Approximate protein sizes are: Gag precursor 71 kDa; N-terminal Gag cleavage product 68 kDa; Pol precursor 127 kDa; reverse transcriptase (RT) 85 kDa; integrase (IN) 40 kDa; Env precursor 130 kDa; surface envelope protein (SU) 80 kDa; transmembrane envelope protein TM 48 kDa; leader peptide (LP)18 kDa; Tas 35 kDa; Bet 60 kDa; and Env-Bet fusion protein 170 kDa. A typical spumavirus genome is about 11.6 kb (Figure 4. Retroviridae) with a genomic organization similar to that of members of the subfamily Orthoretroviridae, as is the mechanism of reverse transcription; this is the basis for placing both subfamilies in the family Retroviridae. There are two genes (tas and bet) that are expressed in cells in addition to gag, pol and env. Tas is a DNA-binding protein with transactivating function. The exact function of the other accessory protein (Bet) is unknown, but it may be involved in viral latency or act as an inhibitor of the APOBEC3 family. The tRNA primer is tRNALys-1,2. The long terminal repeat (LTR) of primate foamy viruses is about 1770 nt, of which the U3 region is about 1400 nt, the R region is about 200 nt and the U5 region is 150 nt. In bovine, equine and feline spumaviruses, the LTR is 950–1400 nt. Spumaviruses make use of two start sites of transcription, R in the LTR and an internal promoter (IP) located upstream of the accessory reading frames within the env gene. The activity of both promoters is Tas-dependent. The additional major criteria distinguishing spumaviruses from members of the other genera are the expression of the Pro and Pol proteins from a spliced subgenomic RNA and the presence of a large amount of reverse transcribed DNA in the virion, this DNA being required for infectivity.
Spumaviruses have a widespread distribution with exogenous spumaviruses found in many mammals (Rethwilm and Lindemann 2013, Khan et al., 2018). Phylogenetic analyses using sequences encoding IN are consistent with the hypothesis that simian foamy viruses have co-evolved with their primate hosts (Khan et al., 2018, Katzourakis et al., 2014, Rethwilm and Bodem 2013, Switzer et al., 2005). Human infections have been documented as a result of rare zoonotic transmissions from non-human primates, but human to human spread has not been observed. Many isolates cause characteristic "foamy" cytopathology in cell culture. No diseases have been associated with spumavirus infection. No oncogene-containing members of the Spumaretrovirinae have been reported. Although a spumaretrovirus receptor has not been identified to date, it is thought that all spumaretroviruses use the same receptor. Spumaretrovirus glycoproteins confer an extremely broad tropism in vitro, including cells and tissues of amphibians, reptiles and mammals. Ancient endogenous proviruses related to the foamyviruses have been reported in the genomes of diverse species, including species with no known exogenous foamyviruses – including various mammals as well as fish, birds, reptiles and amphibians (Katzourakis et al., 2014, Rethwilm and Bodem 2013, Aiewsakun et al., 2019, Chen et al., 2019, Chen et al., 2021, Wei et al., 2019)
Genus demarcation criteria
Viruses are assigned to genera based on natural host range and virus-host co-phylogeny.