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Retrovirology Dec 2017Foamy viruses (FV) are ancient complex retroviruses that differ from orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia virus (MLV) and... (Review)
Review
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.
Topics: Animals; Coinfection; Humans; Retroviridae Infections; Spumavirus; Zoonoses
PubMed: 29197389
DOI: 10.1186/s12977-017-0379-9 -
Viruses Mar 2021Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and... (Review)
Review
Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV-host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.
Topics: APOBEC Deaminases; Animals; Cell Line; Host Microbial Interactions; Humans; Mutation; Primates; Retroviridae Infections; Retroviridae Proteins; Spumavirus
PubMed: 33803830
DOI: 10.3390/v13030504 -
Viruses Sep 2019Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include... (Review)
Review
Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include felines, bovines, and nonhuman primates (NHPs), a large percentage of adults are infected with FVs. For this reason, the effect of FVs on infections with other viruses (co-infections) cannot be easily studied in natural populations. Most of what is known about interactions between FVs and other viruses is based on studies of NHPs in artificial settings such as research facilities. In these settings, there is some indication that FVs can exacerbate infections with lentiviruses such as simian immunodeficiency virus (SIV). Nonhuman primate (NHP) simian FVs (SFVs) have been shown to infect people without any apparent pathogenicity. Humans zoonotically infected with simian foamy virus (SFV) are often co-infected with other viruses. Thus, it is important to know whether SFV co-infections affect human disease.
Topics: Animals; Cats; Coinfection; Humans; Retroviridae; Retroviridae Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Simian foamy virus; Spumavirus; Zoonoses
PubMed: 31569704
DOI: 10.3390/v11100902 -
Viruses Jan 2021Within the family of , foamy viruses (FVs) are unique and unconventional with respect to many aspects in their molecular biology, including assembly and release of... (Review)
Review
Within the family of , foamy viruses (FVs) are unique and unconventional with respect to many aspects in their molecular biology, including assembly and release of enveloped viral particles. Both components of the minimal assembly and release machinery, Gag and Env, display significant differences in their molecular structures and functions compared to the other retroviruses. This led to the placement of FVs into a separate subfamily, the . Here, we describe the molecular differences in FV Gag and Env, as well as Pol, which is translated as a separate protein and not in an orthoretroviral manner as a Gag-Pol fusion protein. This feature further complicates FV assembly since a specialized Pol encapsidation strategy via a tripartite Gag-genome-Pol complex is used. We try to relate the different features and specific interaction patterns of the FV Gag, Pol, and Env proteins in order to develop a comprehensive and dynamic picture of particle assembly and release, but also other features that are indirectly affected. Since FVs are at the root of the retrovirus tree, we aim at dissecting the unique/specialized features from those shared among the and Such analyses may shed light on the evolution and characteristics of virus envelopment since related viruses within the , for instance LTR retrotransposons, are characterized by different levels of envelopment, thus affecting the capacity for intercellular transmission.
Topics: Capsid; Genome, Viral; Host-Pathogen Interactions; Humans; Retroviridae Infections; Spumavirus; Viral Proteins; Virus Assembly; Virus Physiological Phenomena; Virus Release; Virus Replication
PubMed: 33451128
DOI: 10.3390/v13010105 -
Viruses Nov 2019Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans... (Review)
Review
Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e.g., adeno associated and lentiviral vectors) for experimental and therapeutic gene therapy of a variety of monogenetic diseases. Some of the important features of FVVs include the ability to efficiently transduce hematopoietic stem and progenitor cells (HSPCs) from humans, NHPs, canines and rodents. We have successfully used FVV for proof of concept studies to demonstrate safety and efficacy following in-vivo delivery in large animal models. In this review, we will comprehensively discuss FVV based in-vivo gene therapy approaches established in the X-linked severe combined immunodeficiency (SCID-X1) canine model.
Topics: Animals; Cats; Cattle; Disease Models, Animal; Dogs; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cells; Humans; Spumavirus; Stem Cells; Transduction, Genetic; X-Linked Combined Immunodeficiency Diseases
PubMed: 31771194
DOI: 10.3390/v11121091 -
Virology Mar 2018Spumaretroviruses, commonly referred to as foamy viruses, are complex retroviruses belonging to the subfamily Spumaretrovirinae, family Retroviridae, which naturally... (Review)
Review
Spumaretroviruses, commonly referred to as foamy viruses, are complex retroviruses belonging to the subfamily Spumaretrovirinae, family Retroviridae, which naturally infect a variety of animals including nonhuman primates (NHPs). Additionally, cross-species transmissions of simian foamy viruses (SFVs) to humans have occurred following exposure to tissues of infected NHPs. Recent research has led to the identification of previously unknown exogenous foamy viruses, and to the discovery of endogenous spumaretrovirus sequences in a variety of host genomes. Here, we describe an updated spumaretrovirus taxonomy that has been recently accepted by the International Committee on Taxonomy of Viruses (ICTV) Executive Committee, and describe a virus nomenclature that is generally consistent with that used for other retroviruses, such as lentiviruses and deltaretroviruses. This taxonomy can be applied to distinguish different, but closely related, primate (e.g., human, ape, simian) foamy viruses as well as those from other hosts. This proposal accounts for host-virus co-speciation and cross-species transmission.
Topics: Animals; Host Specificity; Humans; Phylogeny; Primates; Retroviridae Infections; Spumavirus
PubMed: 29407373
DOI: 10.1016/j.virol.2017.12.035 -
Microbes and Environments 2021MicroRNAs (miRNAs) classified as non-coding RNAs regulate various metabolic systems and viral life cycles. To date, numerous DNA viruses, many of which are members of...
MicroRNAs (miRNAs) classified as non-coding RNAs regulate various metabolic systems and viral life cycles. To date, numerous DNA viruses, many of which are members of the herpesvirus family, and a relatively small number of RNA viruses, including retroviruses, have been reported to encode and express miRNAs in infected cells. A few retroviruses have been shown to express miRNAs, and foamy viruses (FVs) were initially predicted by computational analyses to possess miRNA-coding regions. Subsequent studies on simian and bovine FVs confirmed the presence of functional and biologically active miRNA expression cassettes. We herein identified feline FV-derived miRNAs using a small RNA deep sequencing ana-lysis. We confirmed their repressive functions on gene expression by dual-luciferase reporter assays. We found that the seed sequences of the miRNAs identified in the present study were conserved among all previously reported FFV isolates. These results suggest that FFV-derived miRNAs play a pivotal role in FFV infection.
Topics: Animals; Cats; Cattle; Gene Expression; MicroRNAs; RNA, Viral; Spumavirus
PubMed: 34776460
DOI: 10.1264/jsme2.ME21055 -
Viruses Aug 2016Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less... (Review)
Review
Compared with orthoretroviruses, our understanding of the molecular and cellular replication mechanism of foamy viruses (FVs), a subfamily of retroviruses, is less advanced. The FV replication cycle differs in several key aspects from orthoretroviruses, which leaves established retroviral models debatable for FVs. Here, we review the general aspect of the FV protein-nucleic acid interactions during virus morphogenesis. We provide a summary of the current knowledge of the FV genome structure and essential sequence motifs required for RNA encapsidation as well as Gag and Pol binding in combination with details about the Gag and Pol biosynthesis. This leads us to address open questions in FV RNA engagement, binding and packaging. Based on recent findings, we propose to shift the point of view from individual glycine-arginine-rich motifs having functions in RNA interactions towards envisioning the FV Gag C-terminus as a general RNA binding protein module. We encourage further investigating a potential new retroviral RNA packaging mechanism, which seems more complex in terms of the components that need to be gathered to form an infectious particle. Additional molecular insights into retroviral protein-nucleic acid interactions help us to develop safer, more specific and more efficient vectors in an era of booming genome engineering and gene therapy approaches.
Topics: Protein Binding; RNA, Viral; Spumavirus; Viral Proteins; Virus Assembly
PubMed: 27589786
DOI: 10.3390/v8090243 -
Viruses Jul 2019Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by... (Review)
Review
Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by the viral enzyme reverse transcriptase (RT). This event is a pivotal step in the life cycle of all retroviruses. In contrast to orthoretroviruses, the domain structure of the mature RT of foamy viruses is different, i.e., it harbors the protease (PR) domain at its N-terminus, thus being a PR-RT. This structural feature has consequences on PR activation, since the enzyme is monomeric in solution and retroviral PRs are only active as dimers. This review focuses on the structural and functional aspects of simian and prototype foamy virus reverse transcription and reverse transcriptase, as well as special features of reverse transcription that deviate from orthoretroviral processes, e.g., PR activation.
Topics: Animals; Humans; Peptide Hydrolases; RNA-Directed DNA Polymerase; Retroviridae Infections; Spumavirus; Viral Proteins
PubMed: 31269675
DOI: 10.3390/v11070598 -
Viruses Jul 2013Successful integration of retroviral DNA into the host chromosome is an essential step for viral replication. The process is mediated by virally encoded integrase (IN)... (Review)
Review
Successful integration of retroviral DNA into the host chromosome is an essential step for viral replication. The process is mediated by virally encoded integrase (IN) and orchestrated by 3'-end processing and the strand transfer reaction. In vitro reaction conditions, such as substrate specificity, cofactor usage, and cellular binding partners for such reactions by the three distinct domains of prototype foamy viral integrase (PFV-IN) have been described well in several reports. Recent studies on the three-dimensional structure of the interacting complexes between PFV-IN and DNA, cofactors, binding partners, or inhibitors have explored the mechanistic details of such interactions and shown its utilization as an important target to develop anti-retroviral drugs. The presence of a potent, non-transferable nuclear localization signal in the PFV C-terminal domain extends its use as a model for investigating cellular trafficking of large molecular complexes through the nuclear pore complex and also to identify novel cellular targets for such trafficking. This review focuses on recent advancements in the structural analysis and in vitro functional aspects of PFV-IN.
Topics: Coenzymes; DNA, Viral; Enzyme Inhibitors; Integrases; Nuclear Localization Signals; Protein Binding; Protein Conformation; Spumavirus
PubMed: 23872492
DOI: 10.3390/v5071850