Integrated cryoEM structure of a spumaretrovirus reveals cross-kingdom evolutionary relationships and the molecular basis for assembly and virus entry

Unique features of foamy virus subfamily include synthesis of Pro/Pol proteins from a separate spliced subgenomic mRNA, leading to their recruitment into virions via Gag C-terminal interactions rather than classical Gag-Pro/Pol fusion.

“(2) synthesis of Pro/Pol proteins from a separate spliced subgenomic mRNA, leading to their recruitment into virions via Gag C-terminal interactions rather than the classical Gag–Pro/Pol (or Gag/Pol) fusion”

Unique features of foamy virus subfamily include initiation of reverse transcription during late stage of virus assembly, leading to presence of fully or partially dsDNA in released virions similar to Hepadnaviruses.

“Some of the unique features of this subfamily include: (1) initiation of reverse transcription of the viral genome during the late stage of virus assembly, leading to the presence of fully or partially dsDNA in the released virions similar to that observed in Hepadnaviruses”

The membrane-targeting signal is found in one of the three glycine-arginine-rich sequences (GR motifs) observed in foamy virus Gag that compensate for the lack of zinc fingers important for encapsidation of gRNA in Orthoretrovirinae as well as Pol incorporation into assembling virions.

“Interestingly, this signal is found in one of the three glycine–arginine-rich rich sequences (GR motifs) observed in foamy virus Gag that compensate for the lack of zinc fingers important for encapsidation of genomic RNA (gRNA) in Orthoretrovirinae as well as Pol incorporation into the assembling virions (Calcraft et al. 2024, Lee et al. 2013, Müllers 2013, Lindemann and Rethwilm 2011, Linial 1999”

Unique features of foamy virus subfamily include an unusual requirement of Env for budding where Gag alone is not sufficient for release of virus particles.

“(3) an unusual requirement of Env for budding where Gag alone is not sufficient for release of virus particles”

Unique features of foamy virus subfamily include a unique Gag protein that lacks classical domains observed in Orthoretrovirinae, such as zinc finger motifs and plasma membrane-targeting signal.

“(4) a unique Gag protein that lacks the classical domains observed in Orthoretrovirinae, such as the zinc finger motifs (cysteine–histidine boxes) and the plasma membrane-targeting signal.”

Absence of the membrane-targeting domain results in intracellular budding of foamy viruses into the endoplasmic/Golgi secretory pathway where they acquire Env, rather than the plasma membrane.

“Absence of the membrane-targeting domain results in intracellular budding of foamy viruses into the endoplasmic/Golgi secretory pathway where they acquire Env, rather than the plasma membrane.”