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Journal articles on the topic 'Foamy virus'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Juretzek, Thomas, Teresa Holm, Kathleen Gärtner, Sylvia Kanzler, Dirk Lindemann, Ottmar Herchenröder, Marcus Picard-Maureau, Matthias Rammling, Martin Heinkelein, and Axel Rethwilm. "Foamy Virus Integration." Journal of Virology 78, no. 5 (March 1, 2004): 2472–77. http://dx.doi.org/10.1128/jvi.78.5.2472-2477.2004.

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ABSTRACT It had been suggested that during integration of spumaretroviruses (foamy viruses) the right (U5) end of the cDNA is processed, while the left (U3) remains uncleaved. We confirmed this hypothesis by sequencing two-long terminal repeat (LTR) circle junctions of unintegrated DNA. Based on an infectious foamy virus molecular clone, a set of constructs harboring mutations at the 5′ end of the U3 region in the 3′ LTR was analyzed for particle export, reverse transcription, and replication. Following transient transfection some mutants were severely impaired in generating infectious virus, while others replicated almost like the wild type. The replication competence of the mutants was unrelated to the cleavability of the newly created U3 end. This became obvious with two mutants both belonging to the high-titer type. One mutant containing a dinucleotide artificially transferred from the right to the left end was trimmed upon integration, while another one with an unrelated dinucleotide in that place was not. The latter construct in particular showed that the canonical TG motif at the beginning of the provirus is not essential for foamy virus integration.

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2

Russell, D. W., and A. D. Miller. "Foamy virus vectors." Journal of virology 70, no. 1 (1996): 217–22. http://dx.doi.org/10.1128/jvi.70.1.217-222.1996.

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3

Kretzschmar, Benedikt, Ali Nowrouzi, Maximilian J. Hartl, Kathleen Gärtner, Tatiana Wiktorowicz, Ottmar Herchenröder, Sylvia Kanzler, et al. "AZT-resistant foamy virus." Virology 370, no. 1 (January 2008): 151–57. http://dx.doi.org/10.1016/j.virol.2007.08.025.

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4

Deyle, David R., Yi Li, Erik M. Olson, and David W. Russell. "Nonintegrating Foamy Virus Vectors." Journal of Virology 84, no. 18 (June 30, 2010): 9341–49. http://dx.doi.org/10.1128/jvi.00394-10.

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ABSTRACT Foamy viruses (FVs), or spumaviruses, are integrating retroviruses that have been developed as vectors. Here we generated nonintegrating foamy virus (NIFV) vectors by introducing point mutations into the highly conserved DD35E catalytic core motif of the foamy virus integrase sequence. NIFV vectors produced high-titer stocks, transduced dividing cells, and did not integrate. Cells infected with NIFV vectors contained episomal vector genomes that consisted of linear, 1-long-terminal-repeat (1-LTR), and 2-LTR circular DNAs. These episomes expressed transgenes, were stable, and became progressively diluted in the dividing cell population. 1-LTR circles but not 2-LTR circles were found in all vector stocks prior to infection. Residual integration of NIFV vectors occurred at a frequency 4 logs lower than that of integrase-proficient FV vectors. Cre recombinase expressed from a NIFV vector mediated excision of both an integrated, floxed FV vector and a gene-targeted neo expression cassette, demonstrating the utility of these episomal vectors. The broad host range and large packaging capacity of NIFV vectors should make them useful for a variety of applications requiring transient gene expression.

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5

Fischer, Nicole, Martin Heinkelein, Dirk Lindemann, Jörg Enssle, Christopher Baum, Evelyn Werder, Hanswalter Zentgraf, Justus G. Müller, and Axel Rethwilm. "Foamy Virus Particle Formation." Journal of Virology 72, no. 2 (February 1, 1998): 1610–15. http://dx.doi.org/10.1128/jvi.72.2.1610-1615.1998.

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ABSTRACT Subgenomic expression plasmids for the so-called human foamy virus (HFV) structural gag, gag/pol, and env genes were constructed and used to analyze foamy virus particle formation by electron microscopy. Expression of an R-U5-gag-pol construct under control of the human cytomegalovirus immediate-early enhancer-promoter resulted in the formation of viral cores with a homogeneous size of approximately 50 nm located in the cytoplasm. Upon coexpression of an envelope construct, particles were observed budding into cytoplasmic vesicles and from the plasma membrane. Expression of the Gag protein precursor pr74 alone led to aberrantly formed viral particles of heterogeneous size and with open cores. Normal-shaped cores were seen after transfection of a construct expressing the p70 gag cleavage product, indicating that p70 gag is able to assemble into capsids. Coexpression of p70 gag and Env resulted in budding virions, ruling out a requirement of the reverse transcriptase for capsid or virion formation. In sharp contrast to other retroviruses, the HFV cores did not spontaneously bud from cellular membranes. Radiochemical labeling followed by protein gel electrophoresis also revealed the intracellular retention of Env-deprived HFV capsids.

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6

Lo, Yung-Tsun, Tao Tian, Peter E. Nadeau, Jeonghae Park, and Ayalew Mergia. "The Foamy Virus Genome Remains Unintegrated in the Nuclei of G1/S Phase-Arrested Cells, and Integrase Is Critical for Preintegration Complex Transport into the Nucleus." Journal of Virology 84, no. 6 (December 23, 2009): 2832–42. http://dx.doi.org/10.1128/jvi.02435-09.

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ABSTRACT Foamy viruses are a member of the spumavirus subfamily of retroviruses with unique mechanisms of virus replication. Foamy virus replication is cell cycle dependent; however, the genome is found in the nuclei of cells arrested in the G1/S phase. Despite the presence of genome in the nuclei of growth-arrested cells, there is no viral gene expression, thus explaining its dependency on cell cycle. This report shows that the foamy virus genome remains unintegrated in G1/S phase-arrested cells. The foamy virus genome is detected by confocal microscopy in the nuclei of both dividing and growth-arrested cells. Alu PCR revealed foamy virus-specific DNA amplification from genomic DNA isolated in cycling cells at 24 h postinfection. In arrested cells no foamy virus DNA band was detected in cells harvested at 1 or 7 days after infection, and a very faint band that is significantly less than DNA amplified from cycling cells was observed at day 15. After these cells were arrested at the G1/S phase for 1, 7, or 15 days they were allowed to cycle, at which time foamy virus-specific DNA amplification was readily observed. Taken together, these results suggest that the foamy virus genome persists in nondividing cells without integrating. We have also established evidence for the first time that the foamy virus genome and Gag translocation into the nucleus are dependent on integrase in cycling cells, implicating the role of integrase in transport of the preintegration complex into the nucleus. Furthermore, despite the presence of a nuclear localization signal sequence in Gag, we observed no foamy virus Gag importation into the nucleus in the absence of integrase.

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7

Verschoor, Ernst J., Susan Langenhuijzen, Saskia van den Engel, Henk Niphuis, Kristin S. Warren, and Jonathan L. Heeney. "Structural and Evolutionary Analysis of an Orangutan Foamy Virus." Journal of Virology 77, no. 15 (August 1, 2003): 8584–87. http://dx.doi.org/10.1128/jvi.77.15.8584-8587.2003.

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ABSTRACT The full-length proviral genome of a foamy virus infecting a Bornean orangutan was amplified, and its sequence was analyzed. Although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus SFVora was evolutionarily equidistant from foamy viruses from other hominoids and from those from Old World monkeys. This finding suggests an independent evolution within its host over a long period of time.

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8

Murray, Shannon M., and Maxine L. Linial. "Simian Foamy Virus Co-Infections." Viruses 11, no. 10 (September 27, 2019): 902. http://dx.doi.org/10.3390/v11100902.

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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.

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9

Hütter, Sylvia, Irena Zurnic, and Dirk Lindemann. "Foamy Virus Budding and Release." Viruses 5, no. 4 (April 10, 2013): 1075–98. http://dx.doi.org/10.3390/v5041075.

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10

Murray, S. M., and M. L. Linial. "Foamy virus infection in primates." Journal of Medical Primatology 35, no. 4-5 (August 2006): 225–35. http://dx.doi.org/10.1111/j.1600-0684.2006.00171.x.

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11

Trobridge, Grant D., and David W. Russell. "Helper-Free Foamy Virus Vectors." Human Gene Therapy 9, no. 17 (November 20, 1998): 2517–25. http://dx.doi.org/10.1089/hum.1998.9.17-2517.

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12

Trobridge, Grant D., and David W. Russell. "Helper-Free Foamy Virus Vectors." Human Gene Therapy 9, no. 17 (November 20, 1998): 2517–25. http://dx.doi.org/10.1089/10430349850019355.

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13

Picard-Maureau, M., F. Kreppel, D. Lindemann, T. Juretzek, O. Herchenröder, A. Rethwilm, S. Kochanek, and M. Heinkelein. "Foamy virus–adenovirus hybrid vectors." Gene Therapy 11, no. 8 (January 15, 2004): 722–28. http://dx.doi.org/10.1038/sj.gt.3302216.

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14

Su, RuiJun, Rency L. Rosales, Martin Lochelt, and Neil C. Josephson. "Transduction of Primate Cells with Feline Foamy Virus Envelope Pseudotyped Prototype Foamy Virus Vectors." Blood 104, no. 11 (November 16, 2004): 5276. http://dx.doi.org/10.1182/blood.v104.11.5276.5276.

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Abstract Because of their genetic and biological similarity to humans, non-human primates are the best pre-clinical models for testing the efficacy and safety of gene therapy systems. However, the presence of endogenous simian foamy virus infection in nearly all non-human primates kept in captivity complicates foamy virus (FV) vector stem cell transduction studies in these animals. A major concern is that repopulating cells exposed to FV vector stocks will elicit an immune response in non-human primate hosts. Though human serum does not inactivate prototype foamy virus (PFV) vectors, a one hour incubation of PFV vector stock in the presence of serum samples from Papio Cynophalus (baboon), Macaca Mulatta (rhesus macaque), or Macaca Fasicularis (long-tailed macaque) results in a 75–100% drop in titer. To overcome this serum mediated inactivation we sought to pseudotype PFV vectors in the feline foamy virus (FFV) envelope. The wild-type envelope from the FUV strain of FFV does not pseudotype our PFV vectors. Therefore we generated chimeras with regions of both the FFV and PFV envelope. By substituting portions of the FFV envelope leader peptide sequence and membrane spanning domain with corresponding PFV envelope regions we generated chimeric envelopes capable of high titer (105–106 FFU/ml) PFV vector production. Serum samples from Macaca Mulatta produced less inactivation of the FFV pseudotyped than the PFV pseudotyped vectors. Furthermore, both the PFV and FFV pseudotyped vectors demonstrated efficient transduction of baboon mesenchymal stem cells (27–43%) and baboon embryonic stem cells (37–40%). However, the FFV pseudotyped vectors transduced both human and baboon CD34+ cells less efficiently than the PFV pseudotyped vectors. We plan to test PFV vectors pseudotyped by other FV envelopes for inactivation by primate serum, and for their ability to transduce primate hematopoietic cells.

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15

Hill, Claire L., Paul D. Bieniasz, and Myra O. McClure. "Properties of human foamy virus relevant to its development as a vector for gene therapy." Journal of General Virology 80, no. 8 (August 1, 1999): 2003–9. http://dx.doi.org/10.1099/0022-1317-80-8-2003.

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The Spumaviridae (foamy viruses) are increasingly being considered as potential vectors for gene therapy, yet little has been documented of their basic cell biology. This study demonstrates that human foamy virus (HFV) has a broad tropism and that the receptor for HFV is expressed not only on many mammalian, but on avian and reptilian cells. Receptor interference assays using an envelope-expressing cell line and a vesicular stomatitis virus/HFV pseudotype virus demonstrate that the cellular receptor is common to all primate members of the genus. The majority of foamy virus particles assemble and remain sequestered intracellularly. A rapid and quantitative method of assaying foamy virus infectivity by reverse transcriptase activity facilitates the use of classical protocols to increase infectious virus titres in vitro to ⩾106 TCID/ml.

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16

Pollok, Karen E., Aaron G. Ernstberger, Scott Goebel, Helmut Hanenberg, and Shanbao Cai. "In Vivo Selection of Murine Long-Term Repopulating Cells Transduced with a Foamy Virus Vector That Expresses MGMTP140K." Blood 106, no. 11 (November 16, 2005): 3061. http://dx.doi.org/10.1182/blood.v106.11.3061.3061.

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Abstract Recombinant foamy virus vectors transduce noncycling and cycling cells, are stable episomally, and integrate into the host genome during cell division. Due to the cytoplasmic stability of this vector, a substantial lag period between transduction and cell division required for provirus integration is possible. Therefore, in transplantation studies that use minimally stimulated hematopoietic stem and progenitor cells (HSC), integration of the foamy virus vector in HSC may occur once HSC divide post-transplantation. We used a foamy virus vector, MD9-P140K-EGFP, that co-expresses a mutant form of O6-methylguanine DNA methyltransferase (MGMTP140K) and the enhanced green fluorescent protein (EGFP) to test the hypothesis that HSC could be transduced with a foamy virus vector and selected in vivo by alkylator-based chemotherapy. We also compared foamy virus transduction and selection to our previously optimized strategy using an oncoretrovirus vector to express MGMTP140K (SF1-P140K-IRES-EGFP). Lineage-depleted bone marrow (BM) from C57BL/6 mice was transduced for 10-16 hours with the foamy virus vector or transduced following a 2-day prestimulation with the oncoretrovirus vector. Data presented are from three primary transplant experiments analyzed over 6 months and one secondary transplantation experiment analyzed for 6 months. The bulk transduction efficiency using the foamy virus vector ranged from 12–25% and the CFU transduction efficiency was 55–57%. Transductions with the oncoretrovirus vectors resulted in similar bulk and CFU transduction efficiencies (55–60%). Similar numbers of progenitor colonies (oncoretrovirus vs. foamy virus) were observed. MGMT activity in pooled progenitor colonies was ~10-fold higher in EGFP+ versus EGFP− colonies. Although similar numbers of CFU were transduced using the two vector systems, significantly different levels of in vivo selection were obtained in primary recipient mice. Consistent with previous studies, selection of oncoretroviral vector-transduced cells resulted in high and sustained levels of EGFP+ cells in the PB and BM in primary and secondary recipient mice (80–99% EGFP+ with 2–3 cycles of 6BG/BCNU). For primary transplants using cells transduced with the foamy virus vector, EGFP expression in the PB peaked at 3 months post-treatment (26.2+/−4.0%) which represented a 4–6 fold increase compared to vehicle-treated mice. However, by 6 months EGFP expression dropped by 3-fold (9+/−1%). Western analysis of MGMT protein levels found in the BM at 6 months post-transplantation also showed a 3-fold decline in expression. In secondary reconstitution experiments, however, flow cytometry and Western analysis of MGMT expression indicated that EGFP expression in foamy virus-transduced HSC no longer correlated with MGMT expression. In fact MGMT expression levels following drug treatment were similar to those found in secondary recipient mice transplanted with oncoretroviral vector-transduced cells, suggesting that stem cells expressing MGMT were selected over time. These data demonstrate that although foamy virus transduction is not as efficient as the more commonly studied oncoretrovirus transduction strategy, a simple overnight protocol can be used to transduce minimally stimulated HSC with a foamy virus vector. These cells can be selected in vivo, can reconstitute mice for up to one year, and can maintain high levels of MGMT expression.

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17

Mergia, Ayalew, and Min Wu. "Characterization of Provirus Clones of Simian Foamy Virus Type 1." Journal of Virology 72, no. 1 (January 1, 1998): 817–22. http://dx.doi.org/10.1128/jvi.72.1.817-822.1998.

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ABSTRACT We have cloned proviral DNA of simian foamy virus type 1 (SFV-1) from linear unintegrated DNA (pSFV-1). Transfection of pSFV-1 induces cytopathology in several cell lines with supernatants from the transfected cell culture containing infectious viral particles. Electron microscopy of the transfected cells revealed foamy virus particles. Deletion analysis of pSFV-1 indicated that the transcriptional transactivator (tas) gene located betweenenv and the long terminal repeat is critical for virus replication, whereas the second open reading frame (ORF-2) in this region is dispensable. Although the tas and ORF-2 regions of foamy viruses have significantly diverged, the results presented here suggested that the gene products have similar functions. Recombinant pSFV-1 containing the cat gene was able to transduce the heterologous gene, indicating the utility of SFV-1 as a vector. An infectious clone of SFV-1 which is distantly related to the human foamy virus will provide a means to understand the biology of this unique group of viruses.

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18

Xu, Fengwen, Juan Tan, Ruikang Liu, Dan Xu, Yue Li, Yunqi Geng, Chen Liang, and Wentao Qiao. "Tetherin inhibits prototypic foamy virus release." Virology Journal 8, no. 1 (2011): 198. http://dx.doi.org/10.1186/1743-422x-8-198.

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19

German, A. C., D. A. Harbour, C. R. Helps, and T. J. Gruffydd-Jones. "Is feline foamy virus really apathogenic?" Veterinary Immunology and Immunopathology 123, no. 1-2 (May 2008): 114–18. http://dx.doi.org/10.1016/j.vetimm.2008.01.035.

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20

Williams, David A. "Foamy Virus Vectors Come of Age." Molecular Therapy 16, no. 4 (April 2008): 635. http://dx.doi.org/10.1038/mt.2008.34.

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21

Trobridge, Grant D. "Foamy virus vectors for gene transfer." Expert Opinion on Biological Therapy 9, no. 11 (September 10, 2009): 1427–36. http://dx.doi.org/10.1517/14712590903246388.

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22

Schweizer, M., Brigitte Corsten, and D. Neumann-Haefelin. "Heterogeneity of primate foamy virus genomes." Archives of Virology 99, no. 1-2 (March 1988): 125–34. http://dx.doi.org/10.1007/bf01311030.

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23

Trobridge, Grant D., Daniel G. Miller, Michael A. Jacobs, James M. Allen, Erik Olson, Hans-Peter Kiem, Rajinder Kaul, and David W. Russell. "Large Scale Analysis of Foamy Virus Vector Integration Sites in Human CD34+ Cells." Blood 104, no. 11 (November 16, 2004): 496. http://dx.doi.org/10.1182/blood.v104.11.496.496.

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Abstract The ability of retroviruses to efficiently integrate into the host cell’s genome has led to their use as gene delivery vehicles for gene therapy. However, integration in the genome can have adverse effects as observed in a gene therapy trial for X-linked SCID using an oncoretroviral vector. Recent studies have shown that an oncoretroviral vector integrated preferentially near transcription start sites and that a lentiviral vector integrated preferentially within genes. Foamy viruses are integrating retroviruses with many properties that distinguish them from onco- or lentiviruses, perhaps the most important characteristic for gene therapy being that they are non-pathogenic. We previously showed that foamy vectors efficiently transduce CD34+ SCID mouse-repopulating cells (SRCs) from human mobilized peripheral blood, demonstrating their potential for hematopoietic stem cell gene therapy. We present here the first large-scale analysis of foamy vector integration sites. Integration sites were determined by infecting human CD34+ cells or normal fibroblasts with a foamy vector carrying a bacterial origin of replication, then rescuing plasmids containing vector provirus-genomic junction sites in bacteria, and sequencing the foamy vector LTR-human genome junctions. Over 1900 unique integration sites in human CD34+ cells and 1000 unique sites in normal human fibroblasts were mapped using the human genome database. The foamy vector did not integrate preferentially into genes. The percentage of integration sites within Refseq genes in human CD34+ cells, human fibroblasts and randomly generated sites was 29, 23, and 32% respectively. Foamy vectors showed only a slight preference for integration within 1 kb 5′ or 3′ of Refseq transcription start sites. In summary, our data show that foamy vectors have a distinct integration site profile relative to oncoretroviral and lentiviral vectors. Future studies will be required to determine if the unique integration site preference of foamy vectors translates into a reduced risk for oncogenesis in gene therapy applications.

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Russell, Rebecca A., Heather L. Wiegand, Michael D. Moore, Alexandra Schäfer, Myra O. McClure, and Bryan R. Cullen. "Foamy Virus Bet Proteins Function as Novel Inhibitors of the APOBEC3 Family of Innate Antiretroviral Defense Factors." Journal of Virology 79, no. 14 (July 2005): 8724–31. http://dx.doi.org/10.1128/jvi.79.14.8724-8731.2005.

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ABSTRACT Foamy viruses are a family of complex retroviruses that establish common, productive infections in a wide range of nonhuman primates. In contrast, humans appear nonpermissive for foamy virus replication, although zoonotic infections do occur. Here we have analyzed the ability of primate and mouse APOBEC3G proteins to inhibit the infectivity of primate foamy virus (PFV) virions produced in their presence. We demonstrate that several APOBEC3 proteins can potently inhibit the infectivity of a PFV-based viral vector. This inhibition correlated with the packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse transcripts. While inhibition of PFV virion infectivity by primate APOBEC3 proteins was largely relieved by coexpression of the PFV Bet protein, a cytoplasmic auxiliary protein of previously uncertain function, Bet failed to relieve inhibition caused by murine APOBEC3. PFV Bet bound to human, but not mouse, APOBEC3 proteins in coexpressing cells, and this binding correlated with the specific inhibition of their incorporation into PFV virions. Of note, both PFV Bet and a second Bet protein, derived from an African green monkey foamy virus, rescued the infectivity of Vif-deficient human immunodeficiency virus type 1 (HIV-1) virions produced in the presence of African green monkey APOBEC3G and blocked the incorporation of this host factor into HIV-1 virion particles. However, neither foamy virus Bet protein reduced APOBEC3 protein expression levels in virion producer cells. While these data identify the foamy virus Bet protein as a functional ortholog of the HIV-1 Vif auxiliary protein, they also indicate that Vif and Bet block APOBEC3 protein function by distinct mechanisms.

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25

Patton, Gillian S., Otto Erlwein, and Myra O. McClure. "Cell-cycle dependence of foamy virus vectors." Journal of General Virology 85, no. 10 (October 1, 2004): 2925–30. http://dx.doi.org/10.1099/vir.0.80210-0.

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Retroviruses differ in the extent to which they are dependent on host-cell proliferation for their replication, an aspect of their replication that impacts on their vector potential. Foamy viruses offer distinct advantages over other retroviruses for development as vectors for gene therapy. A vector derived from the prototypic foamy virus (PFV), formerly known as human foamy virus (HFV), transduced aphidicolin-arrested cells five- to tenfold more efficiently than one derived from murine leukemia virus (MLV), but several-fold less efficiently than a human immunodeficiency virus type 1 (HIV-1) vector. The same relative efficiency was found following transduction of cells that had been arrested by γ-irradiation or with mitomycin C. Cells that were exposed to vector during aphidicolin arrest and were subsequently allowed to cycle were transduced significantly better by PFV than by MLV. Quiescent human CD34+ progenitor cells were transduced as efficiently by PFV as by HIV vectors (40–50 %) when transduction was assayed after the cells were allowed to cycle.

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26

Herchenröder, Ottmar, Martin Löchelt, Florence Buseyne, Antoine Gessain, Marcelo A. Soares, Arifa S. Khan, and Dirk Lindemann. "Twelfth International Foamy Virus Conference—Meeting Report." Viruses 11, no. 2 (February 1, 2019): 134. http://dx.doi.org/10.3390/v11020134.

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The 12th International Foamy Virus Conference took place on August 30–31, 2018 at the Technische Universität Dresden, Dresden, Germany. The meeting included presentations on current research on non-human primate and non-primate foamy viruses (FVs; also called spumaretroviruses) as well as keynote talks on related research areas in retroviruses. The taxonomy of foamy viruses was updated earlier this year to create five new genera in the subfamily, Spumaretrovirinae, based on their animal hosts. Research on viruses from different genera was presented on topics of potential relevance to human health, such as natural infections and cross-species transmission, replication, and viral-host interactions in particular with the immune system, dual retrovirus infections, virus structure and biology, and viral vectors for gene therapy. This article provides an overview of the current state-of-the-field, summarizes the meeting highlights, and presents some important questions that need to be addressed in the future.

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27

Lecellier, Charles-Henri, Manuel Neves, Marie-Lou Giron, Joelle Tobaly-Tapiero, and Ali Saïb. "Further Characterization of Equine Foamy Virus Reveals Unusual Features among the Foamy Viruses." Journal of Virology 76, no. 14 (July 15, 2002): 7220–27. http://dx.doi.org/10.1128/jvi.76.14.7220-7227.2002.

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ABSTRACT Foamy viruses (FVs) are nonpathogenic, widely spread complex retroviruses which have been isolated in nonhuman primates, cattle, cats, and more recently in horses. The equine foamy virus (EFV) was isolated from healthy horses and was characterized by molecular cloning and nucleotide sequence analysis. Here, to further characterize this new FV isolate, the location of the transcriptional cap and poly(A) addition sites as well as the main splice donor and acceptor sites were determined, demonstrating the existence of the specific subgenomic pol mRNA, one specific feature of FVs. Moreover, similar to what has been described for the human foamy virus (HFV), the prototype of FVs, a replication-defective EFV genome was identified during persistent infection. At the protein level, the use of specific antibodies allowed us to determine the size and the subcellular localization of EFV Gag, Env, and Tas, the viral transactivators. While EFV Gag was detected in both the cytoplasm and the nucleus, EFV Env mainly localized in the Golgi complex, in contrast to HFV Env, which is sequestered in the endoplasmic reticulum. In addition, electron microscopy analysis demonstrated that EFV budding occurs at the plasma membrane and not intracellularly, as is the case for primate FVs. Interestingly, EFV Tas was detected both in the nucleus and the cytoplasm of Tas-transfected cells, in contrast to the strict nuclear localization of other FV Tas but similar to the equine infectious anemia virus Tat gene product. Taken together, our results reveal that this new FV isolate exhibits remarkable features among FVs, bringing new insights into the biology of these unconventional retroviruses.

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28

Geiselhart, Verena, Patrizia Bastone, Tore Kempf, Martina Schnölzer, and Martin Löchelt. "Furin-Mediated Cleavage of the Feline Foamy Virus Env Leader Protein." Journal of Virology 78, no. 24 (December 15, 2004): 13573–81. http://dx.doi.org/10.1128/jvi.78.24.13573-13581.2004.

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ABSTRACT The molecular biology of spuma or foamy retroviruses is different from that of the other members of the Retroviridae. Among the distinguishing features, the N-terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader protein Elp, is a component of released, infectious virions and is required for particle budding. The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis. In this study, we investigate the mechanism of Elp release from the Env precursor protein. By a combination of genetic, biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues. The cleavage site fully conforms to the rules for an optimal furin site. Proteolytic processing at the furin cleavage site is required for full infectivity of FFV. However, utilization of other furin proteases and/or cleavage at a suboptimal signal peptidase cleavage site can partially rescue virus viability. In addition, we show that FFV Elp carries an N-linked oligosaccharide that is not conserved among the known foamy viruses.

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29

Olszko, Miles, and Grant Trobridge. "Foamy Virus Vectors for HIV Gene Therapy." Viruses 5, no. 10 (October 22, 2013): 2585–600. http://dx.doi.org/10.3390/v5102585.

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30

Buseyne, Florence, Antoine Gessain, Marcelo Soares, André Santos, Magdalena Materniak-Kornas, Pascale Lesage, Alessia Zamborlini, et al. "Eleventh International Foamy Virus Conference—Meeting Report." Viruses 8, no. 11 (November 23, 2016): 318. http://dx.doi.org/10.3390/v8110318.

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31

Sandstrom, Paul A., Kim Oanh Phan, William M. Switzer, Terry Fredeking, Louisa Chapman, Walid Heneine, and Thomas M. Folks. "Simian foamy virus infection among zoo keepers." Lancet 355, no. 9203 (February 2000): 551–52. http://dx.doi.org/10.1016/s0140-6736(99)05292-7.

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32

Saib, Ali, Martine Canivet, Marie-Louise Giron, Françis Bolgert, Joceline Valla, Sylvie Lagaye, Jorge Périès, and Hugues de Thé. "Human foamy virus infection In myasthenia gravis." Lancet 343, no. 8898 (March 1994): 666. http://dx.doi.org/10.1016/s0140-6736(94)92657-3.

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33

Gärtner, Kathleen, Tatiana Wiktorowicz, Jeonghae Park, Ayalew Mergia, Axel Rethwilm, and Carsten Scheller. "Accuracy estimation of foamy virus genome copying." Retrovirology 6, no. 1 (2009): 32. http://dx.doi.org/10.1186/1742-4690-6-32.

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34

Nestler, U., M. Heinkelein, M. Lücke, J. Meixensberger, W. Scheurlen, A. Kretschmer, and A. Rethwilm. "Foamy virus vectors for suicide gene therapy." Gene Therapy 4, no. 11 (November 1997): 1270–77. http://dx.doi.org/10.1038/sj.gt.3300561.

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35

Roy, Jacqueline, Wolfram Rudolph, Thomas Juretzek, Kathleen Gärtner, Michael Bock, Ottmar Herchenröder, Dirk Lindemann, Martin Heinkelein, and Axel Rethwilm. "Feline Foamy Virus Genome and Replication Strategy." Journal of Virology 77, no. 21 (November 1, 2003): 11324–31. http://dx.doi.org/10.1128/jvi.77.21.11324-11331.2003.

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ABSTRACT Crucial aspects of the foamy virus (FV) replication strategy have so far only been investigated for the prototypic FV (PFV) isolate, which is supposed to be derived from nonhuman primates. To study whether the unusual features of this replication pathway also apply to more-distantly related FVs, we constructed feline FV (FFV) infectious molecular clones and vectors. It is shown by quantitative RNA and DNA PCR analysis that FFV virions contain more RNA than DNA. Full-length linear DNA was found in extracellular FFV by Southern blot analysis. Similar to PFV, azidothymidine inhibition experiments and the transfection of nucleic acids extracted from extracellular FFV indicated that DNA is the functional relevant FFV genome. Unlike PFV, no evidence was found indicating that FFV recycles its DNA into the nucleus.

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36

Saïb, Ali, and Hugues de Thé. "Molecular Biology of the Human Foamy Virus." Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 13 (1996): S254—S260. http://dx.doi.org/10.1097/00042560-199600001-00038.

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37

HACHIYA, Yuma, Kumiko KIMURA, Keisuke OGUMA, Mamiko ONO, Tetsuya HORIKITA, and Hiroshi SENTSUI. "Isolation of bovine foamy virus in Japan." Journal of Veterinary Medical Science 80, no. 10 (2018): 1604–9. http://dx.doi.org/10.1292/jvms.18-0121.

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38

Enssle, J., A. Moebes, M. Heinkelein, M. Panhuysen, B. Mauer, M. Schweizer, D. Neumann-Haefelin, and A. Rethwilm. "An active foamy virus integrase is required for virus replication." Journal of General Virology 80, no. 6 (June 1, 1999): 1445–52. http://dx.doi.org/10.1099/0022-1317-80-6-1445.

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39

Shikova-Lekova, Evelina, Dirk Lindemann, Thomas Pietschmann, Thomas Juretzek, Wolfram Rudolph, Ottmar Herchenröder, Hans R. Gelderblom, and Axel Rethwilm. "Replication-Competent Hybrids between Murine Leukemia Virus and Foamy Virus." Journal of Virology 77, no. 13 (July 1, 2003): 7677–81. http://dx.doi.org/10.1128/jvi.77.13.7677-7681.2003.

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ABSTRACT Replication-competent chimeric retroviruses constructed of members of the two subfamilies of Retroviridae, orthoretroviruses and spumaretroviruses, specifically murine leukemia viruses (MuLV) bearing hybrid MuLV-foamy virus (FV) envelope (env) genes, were characterized. All viruses had the cytoplasmic tail of the MuLV transmembrane protein. In ESL-1, a truncated MuLV leader peptide (LP) was fused to the complete extracellular portion of FV Env, and ESL-2 to -4 contained the complete MuLV-LP followed by N-terminally truncated FV Env decreasing in size. ESL-1 to -4 had an extended host cell range compared to MuLV, induced a cytopathology reminiscent of FVs, and exhibited an ultrastructure that combined the features of the condensed core of MuLV with the prominent surface knobs of FVs. Replication of ESL-2 to -4 resulted in the acquisition of a stop codon at the N terminus of the chimeric Env proteins. This mutation rendered the MuLV-LP nonfunctional and indicated that the truncated FV-LP was sufficient to direct Env synthesis into the secretory pathway. Compared to the parental viruses, the chimeras replicated with only moderate cell-free titers.

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40

Hatama, Shinichi, Kaori Otake, Shinya Omoto, Yasunori Murase, Atushi Ikemoto, Masami Mochizuki, Eiji Takahashi, Harumi Okuyama, and Yoichi Fujii. "Isolation and sequencing of infectious clones of feline foamy virus and a human/feline foamy virus Env chimera." Journal of General Virology 82, no. 12 (December 1, 2001): 2999–3004. http://dx.doi.org/10.1099/0022-1317-82-12-2999.

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Full-length DNAs of the Coleman and S7801 strains (pSKY3.0, pSKY5.0) of infectious feline foamy viruses (FFVs) were cloned and sequenced. Parental viruses, designated SKY3.0 and SKY5.0, were secreted following transfection of Crandell feline kidney (CRFK) cells. Production of the rescued parental viruses was enhanced in the presence of trichostatin A. Amino acid sequence similarities between FFV and human foamy virus (HFV) are extremely low for the envelope protein and capsid antigen, as predicted from the two clones. However, a chimeric FFV clone was constructed with the HFV Env substituted for the FFV Env. The chimeric virus (HFFV, SKY4.0) was able to infect and replicate in CRFK cells as well as in peripheral blood mononuclear cells of cats in vivo. Consequently, the chimeric HFFV may be useful for the creation of FV vectors for gene transfer strategies.

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41

Huang, Fen, Wenhai Yu, and Zhanlong He. "Foamy Virus in the Tree Shrew Tupaia Belangeri Is Highly Related to Simian Foamy Virus in Macaca Mulatta." AIDS Research and Human Retroviruses 29, no. 8 (August 2013): 1177–78. http://dx.doi.org/10.1089/aid.2013.0112.

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42

Wagner, Tobias C., and Jochen Bodem. "Sequence errors in foamy virus sequences in the GenBank database: resequencing of the prototypic foamy virus proviral plasmids." Archives of Virology 162, no. 4 (December 31, 2016): 1141–44. http://dx.doi.org/10.1007/s00705-016-3206-z.

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43

Holzschu, Donald L., Mari A. Delaney, Randall W. Renshaw, and James W. Casey. "The Nucleotide Sequence and Spliced polmRNA Levels of the Nonprimate Spumavirus Bovine Foamy Virus." Journal of Virology 72, no. 3 (March 1, 1998): 2177–82. http://dx.doi.org/10.1128/jvi.72.3.2177-2182.1998.

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ABSTRACT We have determined the complete nucleotide sequence of a replication-competent clone of bovine foamy virus (BFV) and have quantitated the amount of splice pol mRNA processed early in infection. The 544-amino-acid Gag protein precursor has little sequence similarity with its primate foamy virus homologs, but the putative nucleocapsid (NC) protein, like the primate NCs, contains the three glycine-arginine-rich regions that are postulated to bind genomic RNA during virion assembly. The BFV gag and polopen reading frames overlap, with pro and polin the same translational frame. As with the human foamy virus (HFV) and feline foamy virus, we have detected a spliced pol mRNA by PCR. Quantitatively, this mRNA approximates the level of full-length genomic RNA early in infection. The integrase (IN) domain of reverse transcriptase does not contain the canonical HH-CC zinc finger motif present in all characterized retroviral INs, but it does contain a nearby histidine residue that could conceivably participate as a member of the zinc finger. The env gene encodes a protein that is over 40% identical in sequence to the HFV Env. By comparison, the Gag precursor of BFV is predicted to be only 28% identical to the HFV protein.

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44

Winkler, I. G., M. Löchelt, and R. L. P. Flower. "Epidemiology of Feline Foamy Virus and Feline Immunodeficiency Virus Infections in Domestic and Feral Cats: a Seroepidemiological Study." Journal of Clinical Microbiology 37, no. 9 (1999): 2848–51. http://dx.doi.org/10.1128/jcm.37.9.2848-2851.1999.

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Although foamy viruses (Spumaviruses) have repeatedly been isolated from both healthy and diseased cats, cattle, and primates, the primary mode of transmission of those common viruses remains undefined. A database of the feline foamy virus (FeFV) and feline immunodeficiency virus (FIV) antibody status, age, and sex of 389 domestic cats presented to veterinarians was assembled. A similar database for 66 feral (wild) cats was also assembled. That FeFV antibody status reflects infection was validated by PCR. Both FeFV and FIV infection rates were found to gradually increase with age, and over 70% of cats older than 9 years were seropositive for FeFV. In domestic cats, the prevalence of FeFV infection was similar in both sexes. In feral cats, FeFV infection was more prevalent in female cats than in male cats. Although both FeFV and FIV have been reported to be transmitted by biting, the patterns of infection observed are more consistent with an interpretation that transmission of these two retroviruses is not the same. The prevalence of FIV infection is highest in nondesexed male cats, the animals most likely to display aggressive behavior. The gradual increase in the proportion of FeFV-infected animals is consistent with transmission of foamy viruses by intimate social contact between animals and less commonly by aggressive behavior.

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45

Bodem, Jochen, Martin Löchelt, Ping Yang, and Rolf M. Flügel. "Regulation of gene expression by human foamy virus and potentials of foamy viral vectors." Stem Cells 15, S2 (April 1997): 141–47. http://dx.doi.org/10.1002/stem.5530150818.

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46

Schiffer, Cecile, Charles-Henri Lecellier, Abdelkrim Mannioui, Nathalie Felix, Elisabeth Nelson, Jacqueline Lehmann-Che, Marie-Louise Giron, Jean Claude Gluckman, Ali Saib, and Bruno Canque. "Persistent Infection with Primate Foamy Virus Type 1 Increases Human Immunodeficiency Virus Type 1 Cell Binding via a Bet-Independent Mechanism." Journal of Virology 78, no. 20 (October 15, 2004): 11405–10. http://dx.doi.org/10.1128/jvi.78.20.11405-11410.2004.

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ABSTRACT We report that human T cells persistently infected with primate foamy virus type 1 (PFV-1) display an increased capacity to bind human immunodeficiency virus type 1 (HIV-1), resulting in increased cell permissiveness to HIV-1 infection and enhanced cell-to-cell virus transmission. This phenomenon is independent of HIV-1 receptor, CD4, and it is not related to PFV-1 Bet protein expression. Increased virus attachment is specifically inhibited by heparin, indicating that it should be mediated by interactions with heparan sulfate glycosaminoglycans expressed on the target cells. Given that both viruses infect similar animal species, the issue of whether coinfection with primate foamy viruses interferes with the natural course of lentivirus infections in nonhuman primates should be considered.

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47

Aiewsakun, Pakorn, Peter Simmonds, and Aris Katzourakis. "The First Co-Opted Endogenous Foamy Viruses and the Evolutionary History of Reptilian Foamy Viruses." Viruses 11, no. 7 (July 12, 2019): 641. http://dx.doi.org/10.3390/v11070641.

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A recent study reported the discovery of an endogenous reptilian foamy virus (FV), termed ERV-Spuma-Spu, found in the genome of tuatara. Here, we report two novel reptilian foamy viruses also identified as endogenous FVs (EFVs) in the genomes of panther gecko (ERV-Spuma-Ppi) and Schlegel’s Japanese gecko (ERV-Spuma-Gja). Their presence indicates that FVs are capable of infecting reptiles in addition to mammals, amphibians, and fish. Numerous copies of full length ERV-Spuma-Spu elements were found in the tuatara genome littered with in-frame stop codons and transposable elements, suggesting that they are indeed endogenous and are not functional. ERV-Spuma-Ppi and ERV-Spuma-Gja, on the other hand, consist solely of a foamy virus-like env gene. Examination of host flanking sequences revealed that they are orthologous, and despite being more than 96 million years old, their env reading frames are fully coding competent with evidence for strong purifying selection to maintain expression and for them likely being transcriptionally active. These make them the oldest EFVs discovered thus far and the first documented EFVs that may have been co-opted for potential cellular functions. Phylogenetic analyses revealed a complex virus–host co-evolutionary history and cross-species transmission routes of ancient FVs.

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48

Hirata, RK, AD Miller, RG Andrews, and DW Russell. "Transduction of hematopoietic cells by foamy virus vectors." Blood 88, no. 9 (November 1, 1996): 3654–61. http://dx.doi.org/10.1182/blood.v88.9.3654.bloodjournal8893654.

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Foamy viruses are retroviruses of the spumavirus family that are often isolated from primary cultures of primate cells. We previously constructed vectors based on human foamy virus (HFV) and found that they were able to transduce a wide variety of vertebrate cells by integration of the vector genome. Here we show that several types of hematopoietic cells are efficiently transduced by an HFV vector that encodes alkaline phosphatase (AP). These cell types include transformed cell lines and primary hematopoietic progenitors from mice, baboons, and humans. The transduction rates of HFV vectors compare favorably with those obtained by murine leukemia virus vectors, which suggests that HFV vectors may be effective in the treatment of hematologic diseases by gene therapy.

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49

Wu, Min, and Ayalew Mergia. "Packaging Cell Lines for Simian Foamy Virus Type 1 Vectors." Journal of Virology 73, no. 5 (May 1, 1999): 4498–501. http://dx.doi.org/10.1128/jvi.73.5.4498-4501.1999.

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ABSTRACT Foamy viruses are nonpathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. We have previously demonstrated the utility of simian foamy virus type 1 (SFV-1) as a vector system by transient expression assay (M. Wu et al., J. Virol. 72:3451–3454, 1998). In this report, we describe the first stable packaging cell lines for foamy virus vectors based on SFV-1. We developed two packaging cell lines in which the helper DNA is placed under the control of either a constitutive cytomegalovirus (CMV) immediate-early gene or inducible tetracycline promoter for expression. Although the constitutive packaging expressing cell line had a higher copy number of packaging DNA, the inducible packaging cell line produced four times more vector particles. This result suggested that the structural gene products in the constitutively expressing packaging cell line were expressed at a level that is not toxic to the cells, and thus vector production was reduced. The SFV-1 vector in the presence of vesicular stomatitis virus envelope protein G (VSV-G) produced an insignificant level of transduction, indicating that foamy viruses could not be pseudotyped with VSV-G to generate high-titer vectors. The availability of stable packaging cell lines represents a step toward the use of an SFV-1 vector delivery system that will allow scaled-up production of vector stocks for gene therapy.

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Park, Jeonghae, Peter Nadeau, James R. Zucali, Calvin M. Johnson, and Ayalew Mergia. "Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs." Virology 343, no. 2 (December 2005): 275–82. http://dx.doi.org/10.1016/j.virol.2005.08.038.

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