Foamy virus zoonotic infections

Abstract

Background: Foamy viruses (FV) are ancient complex retroviruses that differ from orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia virus (MLV) and comprise a distinct subfamily of retroviruses, the Spumaretrovirinae. FV are ubiquitous in their natural hosts, which include cows, cats, and nonhuman primates (NHP). FV are transmitted mainly through saliva and appear nonpathogenic by themselves, but they may increase morbidity of other pathogens in coinfections.

Conclusions: This review summarizes and discusses what is known about FV infection of natural hosts. It also emphasizes what is known about FV zoonotic infections A large number of studies have revealed that the FV of NHP, simian foamy viruses (SFV), are transmitted to humans who interact with infected NHP. SFV from a variety of NHP establish persistent infection in humans, while bovine foamy virus and feline foamy virus rarely or never do. The possibility of FV recombination and mutation leading to pathogenesis is considered. Since humans can be infected by SFV, a seemingly nonpathogenic virus, there is interest in using SFV vectors for human gene therapy. In this regard, detailed understanding of zoonotic SFV infection is highly relevant.

Keywords: Foamy virus; Nonhuman primates; Retrovirus; Simian foamy virus; Zoonoses.

Fig. 1

The Prototype Foamy Virus (PFV) genome, RNA transcripts, and protein products. a The molecular clone PFV-13 is depicted (Genbank accession no. U21247; 11,954 bp). The proviral long terminal repeats (LTR) are indicated at the 5′ and 3′ ends of the genome. Each LTR is composed of U3, R and U5 sequences. The U3 sequences are from the 3′ end of the viral RNA genome and the U5 sequences are from the 5′ end of the viral RNA genome. The R sequences are repeat sequences that are created during reverse transcription. Horizontal arrows indicate the location of the two viral promoters. The 5′ LTR promoter is blue and indicated as “P” while the internal promoter is green and indicated as “IP”. b The five major PFV mRNAs are shown. The first three mRNAs, including the unspliced genomic RNA and the spliced pol (polymerase) and env (envelope glycoprotein) mRNAs, are expressed from the 5′ LTR promoter and colored different shades of blue. The full-length unspliced RNA (light blue) serves as both the viral genome and the mRNA for the Gag (viral capsid) protein. The two smaller PFV mRNAs encoding the accessory proteins Tas (transactivator) and Bet proteins originate from the IP and are colored dark and light green, respectively. c The shaded boxes indicate the major PFV protein products, Gag, Pol and Env, as well as Tas and Bet. Viral protease-mediated cleavage sites within Gag and Pol are indicated with dashed lines and vertical arrows. The C-terminal P3 domain, released upon Gag cleavage, is indicated. The Pol protein contains PR, the protease domain, RT, the reverse transcriptase domain, and IN, the integrase domain. The Env protein is comprised of LP, leader peptide domain, SU, surface domain and TM, transmembrane domain