Foamy Viruses Are Unconventional Retroviruses

Foamy viruses (FVs; also known as spumaviruses or spumaretroviruses) are classified as one of the genera of the Retroviridae. The FVs, first described in 1954 (18) and isolated in 1971 (1), have been rather neglected relative to their better known retroviral cousins, the type C oncoviruses and lentiviruses. Nonetheless, detailed analyses of this group during the past few years have revealed surprising, and in some cases remarkable, differences from all other retroviruses. In fact, in some respects their replication bridges the gap between retroviruses and the only other family of vertebrate reverse transcriptase (RT)-encoding viruses, the Hepadnaviridae. FVs are widespread, and viruses have been readily isolated from a variety of primate species, including gorillas (7), chimpanzees (33), baboons (13), African green monkeys (64), and numerous others. Recent phylogenetic analysis indicates that FVs have coevolved with their hosts (13). Feline (54, 57) and bovine species (40) are also infected by FV. There are several reports that FVs were detected in other species, such as sea lions (43) and hamsters (38), but no viral isolates are currently available. Studies of both simian foamy virus (SFV) and bovine foamy virus (BFV) in their natural hosts indicate that antiviral antibodies, but not viral infections, are acquired maternally. Animals become infected as young adults, presumably via saliva through biting or licking (13, 44). These viruses are highly cytopathic in many types of cells in tissue culture, leading to rapid syncytium formation, vacuolization of cells (hence the name foamy), and cell death (the biology of FVs is reviewed in reference 37). Human diploid fibroblast cells and baby hamster kidney (BHK) cells are particularly sensitive to FV-induced cytopathic effects. Paradoxically, it is also possible to infect some cell lines, such as cell lines derived from human hematopoietic cells, and obtain persistently infected cultures which produce fairly high titers of replication-competent virus in the absence of cell death (91). The difference in host cell response that potentiates a lytic versus a persistent infection is not yet understood. It is rather curious that a virus which can be exceedingly cytopathic in vitro has not been unequivocally shown to cause disease. A major difference between FVs and the other retroviruses, as well as the hepadnaviruses, is that there is no evidence that FVs are pathogenic in either naturally or accidentally infected hosts. This has kindled interest in the use of FV as a vector for gene transfer (11, 62, 72).