Abstract
All foamy viruses give rise to a strong nuclear staining when infected cells are reacted with sera from infected hosts. This nuclear fluorescence distinguishes foamy viruses from all other retroviruses. The experiments reported here indicate that the foamy virus Gag precursor protein is transiently located in the nuclei of infected cells and this is the likely reason for the typical foamy virus nuclear fluorescence. By using the vaccinia virus expression system, a conserved basic sequence motif in the nucleocapsid domain of foamy virus Gag proteins was identified to be responsible for the nuclear transport of the gag precursor molecule. This motif was also found to be able to direct a heterologous protein, the Gag protein of human immunodeficiency virus, into the nucleus.
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Selected References
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- Achong B. G., Mansell P. W., Epstein M. A., Clifford P. An unusual virus in cultures from a human nasopharyngeal carcinoma. J Natl Cancer Inst. 1971 Feb;46(2):299–307. [PubMed] [Google Scholar]
- Aguzzi A., Wagner E. F., Netzer K. O., Bothe K., Anhauser I., Rethwilm A. Human foamy virus proteins accumulate in neurons and induce multinucleated giant cells in the brain of transgenic mice. Am J Pathol. 1993 Apr;142(4):1061–1071. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bothe K., Aguzzi A., Lassmann H., Rethwilm A., Horak I. Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes. Science. 1991 Aug 2;253(5019):555–557. doi: 10.1126/science.1650034. [DOI] [PubMed] [Google Scholar]
- Bukrinsky M. I., Haggerty S., Dempsey M. P., Sharova N., Adzhubel A., Spitz L., Lewis P., Goldfarb D., Emerman M., Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. doi: 10.1038/365666a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bukrinsky M. I., Sharova N., Dempsey M. P., Stanwick T. L., Bukrinskaya A. G., Haggerty S., Stevenson M. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6580–6584. doi: 10.1073/pnas.89.14.6580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullen B. R. Regulation of human immunodeficiency virus replication. Annu Rev Microbiol. 1991;45:219–250. doi: 10.1146/annurev.mi.45.100191.001251. [DOI] [PubMed] [Google Scholar]
- Dermott E., Clarke J. K., Samuels J. The morphogenesis and classification of bovine syncytial virus. J Gen Virol. 1971 Aug;12(2):105–119. doi: 10.1099/0022-1317-12-2-105. [DOI] [PubMed] [Google Scholar]
- Dermott E., Samuels J. Intrachromosomal location of MK5, a foamy type 1 virus. J Gen Virol. 1973 Apr;19(1):141–143. doi: 10.1099/0022-1317-19-1-141. [DOI] [PubMed] [Google Scholar]
- Eckhardt S. G., Milich D. R., McLachlan A. Hepatitis B virus core antigen has two nuclear localization sequences in the arginine-rich carboxyl terminus. J Virol. 1991 Feb;65(2):575–582. doi: 10.1128/jvi.65.2.575-582.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleming W. A., Clarke J. K. Fluorescence assay of foamy virus. J Gen Virol. 1970 Feb;6(2):277–284. doi: 10.1099/0022-1317-6-2-277. [DOI] [PubMed] [Google Scholar]
- 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]
- Ganem D. Assembly of hepadnaviral virions and subviral particles. Curr Top Microbiol Immunol. 1991;168:61–83. doi: 10.1007/978-3-642-76015-0_4. [DOI] [PubMed] [Google Scholar]
- Garcia-Bustos J., Heitman J., Hall M. N. Nuclear protein localization. Biochim Biophys Acta. 1991 Mar 7;1071(1):83–101. doi: 10.1016/0304-4157(91)90013-m. [DOI] [PubMed] [Google Scholar]
- 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]
- Hooks J. J., Gibbs C. J., Jr, Cutchins E. C., Rogers N. G., Lampert P., Gajdusek D. C. Characteization and distribution of two new foamy viruses isolated from chimpanzees. Arch Gesamte Virusforsch. 1972;38(1):38–55. doi: 10.1007/BF01241354. [DOI] [PubMed] [Google Scholar]
- Hooks J. J., Gibbs C. J., Jr The foamy viruses. Bacteriol Rev. 1975 Sep;39(3):169–185. doi: 10.1128/br.39.3.169-185.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaminsky L. S., McHugh T., Stites D., Volberding P., Henle G., Henle W., Levy J. A. High prevalence of antibodies to acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) in AIDS and related conditions but not in other disease states. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5535–5539. doi: 10.1073/pnas.82.16.5535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller A., Partin K. M., Löchelt M., Bannert H., Flügel R. M., Cullen B. R. Characterization of the transcriptional trans activator of human foamy retrovirus. J Virol. 1991 May;65(5):2589–2594. doi: 10.1128/jvi.65.5.2589-2594.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lanford R. E., Butel J. S. Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen. Cell. 1984 Jul;37(3):801–813. doi: 10.1016/0092-8674(84)90415-x. [DOI] [PubMed] [Google Scholar]
- Lazinski D., Grzadzielska E., Das A. Sequence-specific recognition of RNA hairpins by bacteriophage antiterminators requires a conserved arginine-rich motif. Cell. 1989 Oct 6;59(1):207–218. doi: 10.1016/0092-8674(89)90882-9. [DOI] [PubMed] [Google Scholar]
- Linial M. L., Miller A. D. Retroviral RNA packaging: sequence requirements and implications. Curr Top Microbiol Immunol. 1990;157:125–152. doi: 10.1007/978-3-642-75218-6_5. [DOI] [PubMed] [Google Scholar]
- Loh P. C., Achong B. C., Epstein M. A. Further biological properties of the human syncytial virus. Intervirology. 1977;8(4):204–217. doi: 10.1159/000148896. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Muranyi W., Flügel R. M. Analysis of splicing patterns of human spumaretrovirus by polymerase chain reaction reveals complex RNA structures. J Virol. 1991 Feb;65(2):727–735. doi: 10.1128/jvi.65.2.727-735.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nassal M., Schaller H. Hepatitis B virus replication. Trends Microbiol. 1993 Sep;1(6):221–228. doi: 10.1016/0966-842x(93)90136-f. [DOI] [PubMed] [Google Scholar]
- Nassal M. The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol. 1992 Jul;66(7):4107–4116. doi: 10.1128/jvi.66.7.4107-4116.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Netzer K. O., Rethwilm A., Maurer B., ter Meulen V. Identification of the major immunogenic structural proteins of human foamy virus. J Gen Virol. 1990 May;71(Pt 5):1237–1241. doi: 10.1099/0022-1317-71-5-1237. [DOI] [PubMed] [Google Scholar]
- Netzer K. O., Schliephake A., Maurer B., Watanabe R., Aguzzi A., Rethwilm A. Identification of pol-related gene products of human foamy virus. Virology. 1993 Jan;192(1):336–338. doi: 10.1006/viro.1993.1039. [DOI] [PubMed] [Google Scholar]
- Neumann-Haefelin D., Fleps U., Renne R., Schweizer M. Foamy viruses. Intervirology. 1993;35(1-4):196–207. doi: 10.1159/000150310. [DOI] [PubMed] [Google Scholar]
- Neumann-Haefelin D., Rethwilm A., Bauer G., Gudat F., zur Hausen H. Characterization of a foamy virus isolated from Cercopithecus aethiops lymphoblastoid cells. Med Microbiol Immunol. 1983;172(2):75–86. doi: 10.1007/BF02124508. [DOI] [PubMed] [Google Scholar]
- Pan L. Z., Cheng-Mayer C., Levy J. A. Patterns of antibody response in individuals infected with the human immunodeficiency virus. J Infect Dis. 1987 Apr;155(4):626–632. doi: 10.1093/infdis/155.4.626. [DOI] [PubMed] [Google Scholar]
- 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]
- Rethwilm A., Baunach G., Netzer K. O., Maurer B., Borisch B., ter Meulen V. Infectious DNA of the human spumaretrovirus. Nucleic Acids Res. 1990 Feb 25;18(4):733–738. doi: 10.1093/nar/18.4.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rethwilm A., Darai G., Rösen A., Maurer B., Flügel R. M. Molecular cloning of the genome of human spumaretrovirus. Gene. 1987;59(1):19–28. doi: 10.1016/0378-1119(87)90262-9. [DOI] [PubMed] [Google Scholar]
- Rikkonen M., Peränen J., Käriäinen L. Nuclear and nucleolar targeting signals of Semliki Forest virus nonstructural protein nsP2. Virology. 1992 Aug;189(2):462–473. doi: 10.1016/0042-6822(92)90570-f. [DOI] [PubMed] [Google Scholar]
- Roberts B. L., Richardson W. D., Smith A. E. The effect of protein context on nuclear location signal function. Cell. 1987 Jul 31;50(3):465–475. doi: 10.1016/0092-8674(87)90500-9. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharova N., Bukrinskaya A. p17 and p17-containing gag precursors of input human immunodeficiency virus are transported into the nuclei of infected cells. AIDS Res Hum Retroviruses. 1991 Mar;7(3):303–306. doi: 10.1089/aid.1991.7.303. [DOI] [PubMed] [Google Scholar]
- Temin H. M. Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. Rev Infect Dis. 1988 Mar-Apr;10(2):399–405. doi: 10.1093/clinids/10.2.399. [DOI] [PubMed] [Google Scholar]
- Tuttleman J. S., Pourcel C., Summers J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell. 1986 Nov 7;47(3):451–460. doi: 10.1016/0092-8674(86)90602-1. [DOI] [PubMed] [Google Scholar]