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. 1997 Sep;71(9):6727–6741. doi: 10.1128/jvi.71.9.6727-6741.1997

Characterization of the genome of feline foamy virus and its proteins shows distinct features different from those of primate spumaviruses.

I Winkler 1, J Bodem 1, L Haas 1, M Zemba 1, H Delius 1, R Flower 1, R M Flügel 1, M Löchelt 1
PMCID: PMC191953  PMID: 9261397

Abstract

The genome of the feline foamy virus (FeFV) isolate FUV was characterized by molecular cloning and nucleotide sequence analysis of subgenomic proviral DNA. The overall genetic organization of FeFV and protein sequence comparisons of different FeFV genes with their counterparts from other known foamy viruses confirm that FeFV is a complex foamy virus. However, significant differences exist when FeFV is compared with primate foamy viruses. The FeFV Gag protein is smaller than that of the primate spumaviruses, mainly due to additional MA/CA sequences characteristic of the primate viruses only. Gag protein sequence motifs of the NC domain of primate foamy viruses assumed to be involved in genome encapsidation are not conserved in FeFV. FeFV Gag and Pol proteins were detected with monospecific antisera directed against Gag and Pol domains of the human foamy virus and with antisera from naturally infected cats. Proteolytic processing of the FeFV Gag precursor was incomplete, whereas more efficient proteolytic cleavage of the pre125Pro-Pol protein was observed. The active center of the FeFV protease contains a Gln that replaces an invariant Gly residue at this position in other retroviral proteases. Functional studies on FeFV gene expression directed by the promoter of the long terminal repeat showed that FeFV gene expression was strongly activated by the Bell/Tas transactivator protein. The FeFV Bell/Tas transactivator is about one-third smaller than its counterpart of primate spumaviruses. This difference is also reflected by a limited sequence similarity and only a moderate conservation of structural motifs of the different foamy virus transactivators analyzed.

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Selected References

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  1. Aguzzi A., Marino S., Tschopp R., Rethwilm A. Regulation of expression and pathogenic potential of human foamy virus in vitro and in transgenic mice. Curr Top Microbiol Immunol. 1996;206:243–273. doi: 10.1007/978-3-642-85208-4_13. [DOI] [PubMed] [Google Scholar]
  2. Bartholomä A., Muranyi W., Flügel R. M. Bacterial expression of the capsid antigen domain and identification of native gag proteins in spumavirus-infected cells. Virus Res. 1992 Apr;23(1-2):27–38. doi: 10.1016/0168-1702(92)90065-h. [DOI] [PubMed] [Google Scholar]
  3. Baunach G., Maurer B., Hahn H., Kranz M., Rethwilm A. Functional analysis of human foamy virus accessory reading frames. J Virol. 1993 Sep;67(9):5411–5418. doi: 10.1128/jvi.67.9.5411-5418.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bodem J., Löchelt M., Winkler I., Flower R. P., Delius H., Flügel R. M. Characterization of the spliced pol transcript of feline foamy virus: the splice acceptor site of the pol transcript is located in gag of foamy viruses. J Virol. 1996 Dec;70(12):9024–9027. doi: 10.1128/jvi.70.12.9024-9027.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Campbell M., Renshaw-Gegg L., Renne R., Luciw P. A. Characterization of the internal promoter of simian foamy viruses. J Virol. 1994 Aug;68(8):4811–4820. doi: 10.1128/jvi.68.8.4811-4820.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang J., Lee K. J., Jang K. L., Lee E. K., Baek G. H., Sung Y. C. Human foamy virus Bel1 transactivator contains a bipartite nuclear localization determinant which is sensitive to protein context and triple multimerization domains. J Virol. 1995 Feb;69(2):801–808. doi: 10.1128/jvi.69.2.801-808.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chiswell D. J., Pringle C. R. Feline syncytium-forming virus: DNA provirus size and structure. J Gen Virol. 1979 Jul;44(1):145–152. doi: 10.1099/0022-1317-44-1-145. [DOI] [PubMed] [Google Scholar]
  8. Chiswell D. J., Pringle C. R. Feline syncytium-forming virus: identification of a virion associated reverse transcriptase and electron microscopical observations of infected cells. J Gen Virol. 1979 May;43(2):429–434. doi: 10.1099/0022-1317-43-2-429. [DOI] [PubMed] [Google Scholar]
  9. Chiswell D. J., Pringle C. R. Infectious DNA from cells infected with feline syncytium-forming virus (Spumavirinae). J Gen Virol. 1977 Sep;36(3):551–555. doi: 10.1099/0022-1317-36-3-551. [DOI] [PubMed] [Google Scholar]
  10. Cordonnier A., Casella J. F., Heidmann T. Isolation of novel human endogenous retrovirus-like elements with foamy virus-related pol sequence. J Virol. 1995 Sep;69(9):5890–5897. doi: 10.1128/jvi.69.9.5890-5897.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cullen B. R. Human immunodeficiency virus as a prototypic complex retrovirus. J Virol. 1991 Mar;65(3):1053–1056. doi: 10.1128/jvi.65.3.1053-1056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Davis J. L., Clements J. E. Characterization of a cDNA clone encoding the visna virus transactivating protein. Proc Natl Acad Sci U S A. 1989 Jan;86(2):414–418. doi: 10.1073/pnas.86.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Enssle J., Jordan I., Mauer B., Rethwilm A. Foamy virus reverse transcriptase is expressed independently from the Gag protein. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4137–4141. doi: 10.1073/pnas.93.9.4137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fiedler K., Veit M., Stamnes M. A., Rothman J. E. Bimodal interaction of coatomer with the p24 family of putative cargo receptors. Science. 1996 Sep 6;273(5280):1396–1399. doi: 10.1126/science.273.5280.1396. [DOI] [PubMed] [Google Scholar]
  15. Flower R. L., Wilcox G. E., Cook R. D., Ellis T. M. Detection and prevalence of serotypes of feline syncytial spumaviruses. Arch Virol. 1985;83(1-2):53–63. doi: 10.1007/BF01310964. [DOI] [PubMed] [Google Scholar]
  16. Flügel R. M., Rethwilm A., Maurer B., Darai G. Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes. EMBO J. 1987 Jul;6(7):2077–2084. doi: 10.1002/j.1460-2075.1987.tb02473.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Forsell K., Suomalainen M., Garoff H. Structure-function relation of the NH2-terminal domain of the Semliki Forest virus capsid protein. J Virol. 1995 Mar;69(3):1556–1563. doi: 10.1128/jvi.69.3.1556-1563.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Giron M. L., Colas S., Wybier J., Rozain F., Emanoil-Ravier R. Expression and maturation of human foamy virus Gag precursor polypeptides. J Virol. 1997 Feb;71(2):1635–1639. doi: 10.1128/jvi.71.2.1635-1639.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goepfert P. A., Shaw K. L., Ritter G. D., Jr, Mulligan M. J. A sorting motif localizes the foamy virus glycoprotein to the endoplasmic reticulum. J Virol. 1997 Jan;71(1):778–784. doi: 10.1128/jvi.71.1.778-784.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Goepfert P. A., Wang G., Mulligan M. J. Identification of an ER retrieval signal in a retroviral glycoprotein. Cell. 1995 Aug 25;82(4):543–544. doi: 10.1016/0092-8674(95)90026-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hackett A. J., Pfiester A., Arnstein P. Biological properties of a syncytia-forming agent isolated from domestic cats (feline syncytia-forming virus). Proc Soc Exp Biol Med. 1970 Dec;135(3):899–904. doi: 10.3181/00379727-135-35167. [DOI] [PubMed] [Google Scholar]
  22. Hahn H., Baunach G., Bräutigam S., Mergia A., Neumann-Haefelin D., Daniel M. D., McClure M. O., Rethwilm A. Reactivity of primate sera to foamy virus Gag and Bet proteins. J Gen Virol. 1994 Oct;75(Pt 10):2635–2644. doi: 10.1099/0022-1317-75-10-2635. [DOI] [PubMed] [Google Scholar]
  23. He F., Blair W. S., Fukushima J., Cullen B. R. The human foamy virus Bel-1 transcription factor is a sequence-specific DNA binding protein. J Virol. 1996 Jun;70(6):3902–3908. doi: 10.1128/jvi.70.6.3902-3908.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. He F., Sun J. D., Garrett E. D., Cullen B. R. Functional organization of the Bel-1 trans activator of human foamy virus. J Virol. 1993 Apr;67(4):1896–1904. doi: 10.1128/jvi.67.4.1896-1904.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Herchenröder O., Renne R., Loncar D., Cobb E. K., Murthy K. K., Schneider J., Mergia A., Luciw P. A. Isolation, cloning, and sequencing of simian foamy viruses from chimpanzees (SFVcpz): high homology to human foamy virus (HFV). Virology. 1994 Jun;201(2):187–199. doi: 10.1006/viro.1994.1285. [DOI] [PubMed] [Google Scholar]
  26. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  27. Jackson M. R., Nilsson T., Peterson P. A. Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J. 1990 Oct;9(10):3153–3162. doi: 10.1002/j.1460-2075.1990.tb07513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jordan I., Enssle J., Güttler E., Mauer B., Rethwilm A. Expression of human foamy virus reverse transcriptase involves a spliced pol mRNA. Virology. 1996 Oct 1;224(1):314–319. doi: 10.1006/viro.1996.0534. [DOI] [PubMed] [Google Scholar]
  29. Keller A., Garrett E. D., Cullen B. R. The Bel-1 protein of human foamy virus activates human immunodeficiency virus type 1 gene expression via a novel DNA target site. J Virol. 1992 Jun;66(6):3946–3949. doi: 10.1128/jvi.66.6.3946-3949.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Konvalinka J., Löchelt M., Zentgraf H., Flügel R. M., Kräusslich H. G. Active foamy virus proteinase is essential for virus infectivity but not for formation of a Pol polyprotein. J Virol. 1995 Nov;69(11):7264–7268. doi: 10.1128/jvi.69.11.7264-7268.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991 Oct 25;266(30):19867–19870. [PubMed] [Google Scholar]
  32. Kukolj G., Jones K. S., Skalka A. M. Subcellular localization of avian sarcoma virus and human immunodeficiency virus type 1 integrases. J Virol. 1997 Jan;71(1):843–847. doi: 10.1128/jvi.71.1.843-847.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kupiec J. J., Kay A., Hayat M., Ravier R., Périès J., Galibert F. Sequence analysis of the simian foamy virus type 1 genome. Gene. 1991 May 30;101(2):185–194. doi: 10.1016/0378-1119(91)90410-d. [DOI] [PubMed] [Google Scholar]
  34. Kögel D., Aboud M., Flügel R. M. Molecular biological characterization of the human foamy virus reverse transcriptase and ribonuclease H domains. Virology. 1995 Oct 20;213(1):97–108. doi: 10.1006/viro.1995.1550. [DOI] [PubMed] [Google Scholar]
  35. Lee A. H., Lee K. J., Kim S., Sung Y. C. Transactivation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by the human foamy virus bel1 protein requires a specific DNA sequence. J Virol. 1992 May;66(5):3236–3240. doi: 10.1128/jvi.66.5.3236-3240.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lee C. W., Chang J., Lee K. J., Sung Y. C. The Bel1 protein of human foamy virus contains one positive and two negative control regions which regulate a distinct activation domain of 30 amino acids. J Virol. 1994 Apr;68(4):2708–2719. doi: 10.1128/jvi.68.4.2708-2719.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Löchelt M., Flügel R. M., Aboud M. The human foamy virus internal promoter directs the expression of the functional Bel 1 transactivator and Bet protein early after infection. J Virol. 1994 Feb;68(2):638–645. doi: 10.1128/jvi.68.2.638-645.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Löchelt M., Flügel R. M. The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and not as a Gag-Pol fusion protein. J Virol. 1996 Feb;70(2):1033–1040. doi: 10.1128/jvi.70.2.1033-1040.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Löchelt M., Muranyi W., Flügel R. M. Human foamy virus genome possesses an internal, Bel-1-dependent and functional promoter. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7317–7321. doi: 10.1073/pnas.90.15.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Löchelt M., Zentgraf H., Flügel R. M. Construction of an infectious DNA clone of the full-length human spumaretrovirus genome and mutagenesis of the bel 1 gene. Virology. 1991 Sep;184(1):43–54. doi: 10.1016/0042-6822(91)90820-2. [DOI] [PubMed] [Google Scholar]
  41. Mahnke C., Löchelt M., Bannert H., Flügel R. M. Specific enzyme-linked immunosorbent assay for the detection of antibodies to the human spumavirus. J Virol Methods. 1990 Jul;29(1):13–22. doi: 10.1016/0166-0934(90)90003-x. [DOI] [PubMed] [Google Scholar]
  42. Maurer B., Bannert H., Darai G., Flügel R. M. Analysis of the primary structure of the long terminal repeat and the gag and pol genes of the human spumaretrovirus. J Virol. 1988 May;62(5):1590–1597. doi: 10.1128/jvi.62.5.1590-1597.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Mergia A., Luciw P. A. Replication and regulation of primate foamy viruses. Virology. 1991 Oct;184(2):475–482. doi: 10.1016/0042-6822(91)90417-a. [DOI] [PubMed] [Google Scholar]
  44. Mergia A., Shaw K. E., Lackner J. E., Luciw P. A. Relationship of the env genes and the endonuclease domain of the pol genes of simian foamy virus type 1 and human foamy virus. J Virol. 1990 Jan;64(1):406–410. doi: 10.1128/jvi.64.1.406-410.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mergia A. Simian foamy virus type 1 contains a second promoter located at the 3' end of the env gene. Virology. 1994 Feb 15;199(1):219–222. doi: 10.1006/viro.1994.1114. [DOI] [PubMed] [Google Scholar]
  46. Pahl A., Flügel R. M. Endonucleolytic cleavages and DNA-joining activities of the integration protein of human foamy virus. J Virol. 1993 Sep;67(9):5426–5434. doi: 10.1128/jvi.67.9.5426-5434.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Renne R., Friedl E., Schweizer M., Fleps U., Turek R., Neumann-Haefelin D. Genomic organization and expression of simian foamy virus type 3 (SFV-3). Virology. 1992 Feb;186(2):597–608. doi: 10.1016/0042-6822(92)90026-l. [DOI] [PubMed] [Google Scholar]
  48. Renshaw R. W., Casey J. W. Transcriptional mapping of the 3' end of the bovine syncytial virus genome. J Virol. 1994 Feb;68(2):1021–1028. doi: 10.1128/jvi.68.2.1021-1028.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rethwilm A. Regulation of foamy virus gene expression. Curr Top Microbiol Immunol. 1995;193:1–24. doi: 10.1007/978-3-642-78929-8_1. [DOI] [PubMed] [Google Scholar]
  50. Rhee S. S., Hunter E. A single amino acid substitution within the matrix protein of a type D retrovirus converts its morphogenesis to that of a type C retrovirus. Cell. 1990 Oct 5;63(1):77–86. doi: 10.1016/0092-8674(90)90289-q. [DOI] [PubMed] [Google Scholar]
  51. Riggs J. L., Oshirls, Taylor D. O., Lennette E. H. Syncytium-forming agent isolated from domestic cats. Nature. 1969 Jun 21;222(5199):1190–1191. doi: 10.1038/2221190a0. [DOI] [PubMed] [Google Scholar]
  52. Rost B., Sander C. Combining evolutionary information and neural networks to predict protein secondary structure. Proteins. 1994 May;19(1):55–72. doi: 10.1002/prot.340190108. [DOI] [PubMed] [Google Scholar]
  53. Schliephake A. W., Rethwilm A. Nuclear localization of foamy virus Gag precursor protein. J Virol. 1994 Aug;68(8):4946–4954. doi: 10.1128/jvi.68.8.4946-4954.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Sohn K., Orci L., Ravazzola M., Amherdt M., Bremser M., Lottspeich F., Fiedler K., Helms J. B., Wieland F. T. A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding. J Cell Biol. 1996 Dec;135(5):1239–1248. doi: 10.1083/jcb.135.5.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sommerville J., Ladomery M. Masking of mRNA by Y-box proteins. FASEB J. 1996 Mar;10(4):435–443. doi: 10.1096/fasebj.10.4.8647342. [DOI] [PubMed] [Google Scholar]
  56. Tomonaga K., Mikami T. Molecular biology of the feline immunodeficiency virus auxiliary genes. J Gen Virol. 1996 Aug;77(Pt 8):1611–1621. doi: 10.1099/0022-1317-77-8-1611. [DOI] [PubMed] [Google Scholar]
  57. Waters A. K., De Parseval A. P., Lerner D. L., Neil J. C., Thompson F. J., Elder J. H. Influence of ORF2 on host cell tropism of feline immunodeficiency virus. Virology. 1996 Jan 1;215(1):10–16. doi: 10.1006/viro.1996.0002. [DOI] [PubMed] [Google Scholar]
  58. Yamamoto J. K., Sparger E., Ho E. W., Andersen P. R., O'Connor T. P., Mandell C. P., Lowenstine L., Munn R., Pedersen N. C. Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. Am J Vet Res. 1988 Aug;49(8):1246–1258. [PubMed] [Google Scholar]
  59. Yu S. F., Baldwin D. N., Gwynn S. R., Yendapalli S., Linial M. L. Human foamy virus replication: a pathway distinct from that of retroviruses and hepadnaviruses. Science. 1996 Mar 15;271(5255):1579–1582. doi: 10.1126/science.271.5255.1579. [DOI] [PubMed] [Google Scholar]
  60. Yu S. F., Edelmann K., Strong R. K., Moebes A., Rethwilm A., Linial M. L. The carboxyl terminus of the human foamy virus Gag protein contains separable nucleic acid binding and nuclear transport domains. J Virol. 1996 Dec;70(12):8255–8262. doi: 10.1128/jvi.70.12.8255-8262.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yu S. F., Linial M. L. Analysis of the role of the bel and bet open reading frames of human foamy virus by using a new quantitative assay. J Virol. 1993 Nov;67(11):6618–6624. doi: 10.1128/jvi.67.11.6618-6624.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Zenger E., Brown W. C., Song W., Wolf A. M., Pedersen N. C., Longnecker M., Li J., Collisson E. W. Evaluation of cofactor effect of feline syncytium-forming virus on feline immunodeficiency virus infection. Am J Vet Res. 1993 May;54(5):713–718. [PubMed] [Google Scholar]
  63. Zou J. X., Luciw P. A. The transcriptional transactivator of simian foamy virus 1 binds to a DNA target element in the viral internal promoter. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):326–330. doi: 10.1073/pnas.93.1.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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