Heparan Sulfate Is an Attachment Factor for Foamy Virus Entry

Plochmann, Kathrin; Horn, Anne; Gschmack, Eva; Armbruster, Nicole; Krieg, Jennifer; Wiktorowicz, Tatiana; Weber, Conrad; Stirnnagel, Kristin; Lindemann, Dirk; Rethwilm, Axel; Scheller, Carsten

doi:10.1128/jvi.00051-12

Cited by 53 publications

(53 citation statements)

References 53 publications

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“…Interestingly, when we tested several other human cell lines we found that all FV tested showed varying abilities to replicate, and in some instances they were unable to replicate at all. Given that the proteoglycan heparin sulfate is known to be an important factor for FV attachment and entry, it is presumed that almost all human cells are permissive for FV entry (53). Our results provide indirect evidence that there are likely host factors involved in either supporting or inhibiting FV replication in humans.…”

Section: Discussionsupporting

confidence: 56%

New World Simian Foamy Virus Infections In Vivo and In Vitro

Stenbak

Craig

Ivanov

et al. 2014

J Virol

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e Foamy viruses (FV) are complex retroviruses that naturally infect all nonhuman primates (NHP) studied to date. Zoonotic transmission of Old World NHP simian foamy viruses (SFV) has been documented, leading to nonpathogenic persistent infections. To date, there have been no reports concerning zoonotic transmission of New World monkey (NWM) SFV to humans and resulting infection. In this study, we developed a Western blot assay to detect antibodies to NWM SFV, a nested PCR assay to detect NWM SFV DNA, and a ␤-galactosidase-containing indicator cell line to assay replication of NWM SFV. Using these tools, we analyzed the plasma and blood of 116 primatologists, of whom 69 had reported exposures to NWM. While 8 of the primatologists tested were seropositive for SFV from a NWM, the spider monkey, none had detectable levels of viral DNA in their blood. We found that SFV isolated from three different species of NWM replicated in some, but not all, human cell lines. From our data, we conclude that while humans exposed to NWM SFV produce antibodies, there is no evidence for long-term viral persistence. Foamy viruses (FV) are unusual complex retroviruses that infect cattle, horses, cats, and all species of nonhuman primates (NHP) examined to date (reviewed in reference 1). Simian foamy viruses (SFV) can cause life-long infections in natural hosts without any apparent pathogenicity (2). In cell culture models, SFV can establish latent infections in some cell types and lytic infections in others, resulting in cytopathic effects (CPE) that include syncytium formation (reviewed in reference 3). In infected macaques, FV DNA is found in almost all tissues, while FV RNA and replicating virus are limited to the superficial epithelial cells of the oral mucosa in immunocompetent animals (4, 5). Consistent with the site of viral replication detected in vivo, it is thought that FV are transmitted via saliva, through grooming, biting, and other behaviors. Studies of natural transmission suggest that infant and young NHP are resistant to infection, presumably because of passive immunity from maternal antibodies, but typically (for macaques) become infected by 3 years of age (6). Epidemiological studies indicate that SFV seroprevalence can reach up to 100% in adults (reviewed in reference 7).Although FV do not naturally infect humans, SFV have been found to be zoonotically transmitted, most likely through contact with saliva from an infected NHP. Several studies have documented the transmission of SFV to humans who interact directly with Old World (OW) NHP, including Cercopithicus species, baboons, macaques, mandrills, gorillas, and chimpanzees (reviewed in reference 7). SFV antibody-positive humans have been found in a variety of natural settings, including people in Asia who live in areas with free-ranging macaques, villagers in Gabon with known exposure to NHP, and a population of hunters in Cameroon with bites from Old World NHP (6,(8)(9)(10)(11). SFV antibody-positive humans have also been documented in various laboratory, veterina...

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Section: Discussionsupporting

confidence: 56%

New World Simian Foamy Virus Infections In Vivo and In Vitro

Stenbak

Craig

Ivanov

et al. 2014

J Virol

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“…SFV uses heparin sulfate to attach to target cells (47,48), but the receptor for SFV is still unknown (64). Interference studies showed that one cellular receptor is used by all SFVs (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

“…The broad tropism of SFV suggests a ubiquitous cellular receptor (42,43). While all SFVs seem to use the same cellular receptor (44)(45)(46), only heparin sulfate has been identified as an attachment factor so far (47,48).…”

mentioning

confidence: 99%

Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa

Richard

Rua

Betsem

et al. 2015

J Virol

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Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. IMPORTANCESFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to humans. These variants differ greatly in the SU region that corresponds to the part of the Env protein in contact with the environment. These variants may have emerged through recombination between SFV strains infecting different NHP species.

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“…The FV Env trimers thereby appear to cluster into metastable hexamers with a central depression, thus giving the characteristic prominent extracellular spike structures observed on electron micrographs of FV particles [5]. Currently it is unknown whether this hexameric organization of the FV Env glycoprotein complexes is essential for host cell receptor recognition, as cellular attachment and entry factors are poorly characterized and non-permissive cells were only recently identified [6,7,8]. The first part of this review will focus on our current knowledge of molecular determinants of initial virus-host interactions that allow for FV attachment and glycoprotein-dependent release of capsids into the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Early Events in Foamy Virus—Host Interaction and Intracellular Trafficking

Berka

Hamann

Lindemann

2013

Viruses

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Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.

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Heparan Sulfate Is an Attachment Factor for Foamy Virus Entry

Cited by 53 publications

References 53 publications

New World Simian Foamy Virus Infections In Vivo and In Vitro

New World Simian Foamy Virus Infections In Vivo and In Vitro

Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa

Early Events in Foamy Virus—Host Interaction and Intracellular Trafficking

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