Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

Abstract

The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs.

Infection with Foamy Virus in Wild Ruminants—Evidence for a New Virus Reservoir?

“…In BFV, free and mixed grazing of cattle and deer in rural areas may lead to BFV transmission as has been well documented for small ruminant lentiviruses in France by Erhouma and others [30], where close contact between wild ibex and goats at pastures led to small ruminant lentiviruses infections in wild animals, or for BoHV-1 which was detected in cervid populations in Germany and in Poland [24,42]. BFV transmission through saliva has been described as the most frequent route of transmission in natural conditions [3,10]; however, our own studies showed that the isolation of BFV from saliva is possible only from a small percentage of animals [32]. Unpublished data also showed that, in contrast to SFV or FFV, BFV viral load in the saliva of naturally and experimentally infected cows is very variable, from quite high to undetectable in some BFV-positive animals, but the explanation for this phenomenon is still unclear.…”

“…Most known FVs are highly prevalent in their hosts. For instance, the prevalence of BFV among cattle ranges between 7% and 50% of cattle worldwide, while in Poland it reaches over 30% (see for summary [10]). Transmission of BFV is suggested to occur through saliva, and, therefore, there is likely to be a risk of its spread through shared grazing areas or direct social or environmental contacts [5,6].…”

“…The most likely routes of FV transmission are via the transfer of blood and saliva and social interactions [3,[5][6][7]. Over the last 60 years, FVs have been isolated and described in different species of non-human primates (Simian FVs (SFVs)) [8], as well as in cattle (Bovine FV (BFV), in the past also called bovine syncytial virus (BSV)) [9,10], cats (Feline FV (FFV)) and horses (Equine FV (EFV)) [3,11]. Several other non-primate FVs have been reported as having been isolated or simply described in sea lions, leopards, sheep, goats, hamsters, and American bison on the basis of cross-antigenicity with known FV, specific cytopathic effects or electron microscopy analyses [10,[12][13][14][15][16].…”

“…Over the last 60 years, FVs have been isolated and described in different species of non-human primates (Simian FVs (SFVs)) [8], as well as in cattle (Bovine FV (BFV), in the past also called bovine syncytial virus (BSV)) [9,10], cats (Feline FV (FFV)) and horses (Equine FV (EFV)) [3,11]. Several other non-primate FVs have been reported as having been isolated or simply described in sea lions, leopards, sheep, goats, hamsters, and American bison on the basis of cross-antigenicity with known FV, specific cytopathic effects or electron microscopy analyses [10,[12][13][14][15][16]. Although FVs can be commonly isolated from infected animals, no disease has been associated with infections and, therefore, FVs are recognized as apathogenic on their own [17,18].…”

Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction

“…Foamy viruses (FV), or spumaretroviruses, comprise five genera of the Spumaretrovirinae [11]. FVs are characterized by several unique features in their molecular biology and replication strategy compared to the Orthoretrovirinae encompassing the remaining majority of the retrovirus family including the deltaretrovirus BLV [11][12][13][14][15]. Due to their apathogenicity, broad range of susceptible host cells, and other features, FVs are promising candidates for novel virus vectors [16].…”