Bovine foamy virus

The process by which foamy viruses enter a cell lacks certain levels of characterization, however it is known that the virus particle first attaches to its host using the SU glycoprotein present on its envelope.[8] The binding receptor for foamy viruses is not entirely know, however it is known that the virus is capable of infecting a board spectrum of cells, meaning the binding receptor must be quite prevalent in most forms of cells.[9] Research has shown that the most likely candidate for a common receptor is heparan sulfate (HS), an extremely common glycosaminoglycan (GAG) present on the ECM of many cells.[9]

Once internalized, the virus particle must fuse with the internal vesicle and allow its genetic material to escape into the cytoplasm. Viral fusion is mediated through the TM glycoprotein. The fusion process is imitated when the TM protein is cleaved by the changing levels of pH which in turns creates a conformation change in the protein, fusing the membrane of the virus with the internal vesicle.[9]

Once the viral particle has delivered its genetic material safely into the cytoplasm of its host, one of two things will occur. If the genetic payload of the virion was double stranded DNA, the viral DNA will directly integrate into the host's genome via the viral enzyme integrase.[1][7] If the payload was ssRNA the RNA is first copied into sdDNA via reverse transcriptase and then integrated randomly into the host genome by integrase. The host cell then performs its natural replication functions, however while doing so it transcribes viral RNA which is then translated into precursor polyproteins.[7] At this point in the cycle, if any viral RNA is remaining, it will be transcribed into dsDNA, however it is too late to be integrated into the host-cell genome. This dsDNA is then randomly packaged into newly formed virions along with the ssRNA. From this point the viral particles begin to bud. Most bud into the endoplasmic reticulum which are then packaged and distributed to other cells. Some particles manage to escape through the membrane but this number is usually quite low.[7][10][11]

Being a spumavirus, bovine foamy virus has a unique life cycle, even when compared to other retroviruses. One of these differences is the mechanism used in the budding process. Rather than budding through the plasma membrane like a more traditional retrovirus, BFV and other foamy viruses bud using the endoplasmic reticulum. Another facet of BFV that makes it unique among other retroviruses is how late in the replication cycle reverse-transcription takes place. This results in some of virions containing DNA rather than typical RNA. This also results in some level of integration into the host cell DNA in uncommon ways.[10] For this reason, scientists have likened foamy viruses to viruses of the family Hepadnaviridae. Foamy viruses also contain structural genes that are distinct to their particular genus. The Gag protein is not always correctly cleaved into the mature form of the viral protein, as seen in other members of retrovirdae, which leads to the overall immature morphology of FV.[1] The Env budding associated protein found in the transmembrane domain of the viron contains an endoplasmic reticulum retention signal which contributes to its ability to bud into the ER.[1][11]