Abstract
The pathways used in the transport of retroviral genomes to the nucleus are poorly identified. Analyzing the intracellular localization of incoming foamy viruses, we have found that the Gag antigens and the viral genome accumulate in a distinct perinuclear domain identified as the centrosome. Colchicine treatment completely abolished pericentriolar targeting of human foamy virus (HFV) proteins, suggesting a role for microtubules in the transport of the incoming viral proteins to the centrioles. Finally, we demonstrate that, similarly to human immunodeficiency virus DNA, HFV DNA can enter the nucleus of G1/S-phase-arrested cells, although no viral gene expression can be observed. Recent observations have demonstrated that foamy viruses have several features not shared by other retroviruses. The intracellular route of the incoming Gag antigens may constitute a new specificity of this class of viruses.
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- Bailly E., Dorée M., Nurse P., Bornens M. p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. EMBO J. 1989 Dec 20;8(13):3985–3995. doi: 10.1002/j.1460-2075.1989.tb08581.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bieniasz P. D., Weiss R. A., McClure M. O. Cell cycle dependence of foamy retrovirus infection. J Virol. 1995 Nov;69(11):7295–7299. doi: 10.1128/jvi.69.11.7295-7299.1995. [DOI] [PMC free article] [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]
- Chun T. W., Finzi D., Margolick J., Chadwick K., Schwartz D., Siliciano R. F. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat Med. 1995 Dec;1(12):1284–1290. doi: 10.1038/nm1295-1284. [DOI] [PubMed] [Google Scholar]
- Dales S., Chardonnet Y. Early events in the interaction of adenoviruses with HeLa cells. IV. Association with microtubules and the nuclear pore complex during vectorial movement of the inoculum. Virology. 1973 Dec;56(2):465–483. doi: 10.1016/0042-6822(73)90050-0. [DOI] [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]
- Gallay P., Swingler S., Aiken C., Trono D. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell. 1995 Feb 10;80(3):379–388. doi: 10.1016/0092-8674(95)90488-3. [DOI] [PubMed] [Google Scholar]
- Gallay P., Swingler S., Song J., Bushman F., Trono D. HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell. 1995 Nov 17;83(4):569–576. doi: 10.1016/0092-8674(95)90097-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Giron M. L., Rozain F., Debons-Guillemin M. C., Canivet M., Peries J., Emanoil-Ravier R. Human foamy virus polypeptides: identification of env and bel gene products. J Virol. 1993 Jun;67(6):3596–3600. doi: 10.1128/jvi.67.6.3596-3600.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Jasmin B. J., Cartaud J., Bornens M., Changeux J. P. Golgi apparatus in chick skeletal muscle: changes in its distribution during end plate development and after denervation. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7218–7222. doi: 10.1073/pnas.86.18.7218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kristensson K., Lycke E., Röyttä M., Svennerholm B., Vahlne A. Neuritic transport of herpes simplex virus in rat sensory neurons in vitro. Effects of substances interacting with microtubular function and axonal flow [nocodazole, taxol and erythro-9-3-(2-hydroxynonyl)adenine]. J Gen Virol. 1986 Sep;67(Pt 9):2023–2028. doi: 10.1099/0022-1317-67-9-2023. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lewis P. F., Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol. 1994 Jan;68(1):510–516. doi: 10.1128/jvi.68.1.510-516.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luftig R. B., Lupo L. D. Viral interactions with the host-cell cytoskeleton: the role of retroviral proteases. Trends Microbiol. 1994 May;2(5):178–182. doi: 10.1016/0966-842x(94)90669-6. [DOI] [PubMed] [Google Scholar]
- Miles B. D., Luftig R. B., Weatherbee J. A., Weihing R. R., Weber J. Quantitation of the interaction between adenovirus types 2 and 5 and microtubules inside infected cells. Virology. 1980 Aug;105(1):265–269. doi: 10.1016/0042-6822(80)90177-4. [DOI] [PubMed] [Google Scholar]
- Naldini L., Blömer U., Gallay P., Ory D., Mulligan R., Gage F. H., Verma I. M., Trono D. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996 Apr 12;272(5259):263–267. doi: 10.1126/science.272.5259.263. [DOI] [PubMed] [Google Scholar]
- Puvion-Dutilleul F., Puvion E. Ultrastructural localization of defined sequences of viral RNA and DNA by in situ hybridization of biotinylated DNA probes on sections of herpes simplex virus type 1 infected cells. J Electron Microsc Tech. 1991 Aug;18(4):336–353. doi: 10.1002/jemt.1060180403. [DOI] [PubMed] [Google Scholar]
- 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]
- Risco C., Menéndez-Arias L., Copeland T. D., Pinto da Silva P., Oroszlan S. Intracellular transport of the murine leukemia virus during acute infection of NIH 3T3 cells: nuclear import of nucleocapsid protein and integrase. J Cell Sci. 1995 Sep;108(Pt 9):3039–3050. doi: 10.1242/jcs.108.9.3039. [DOI] [PubMed] [Google Scholar]
- Roth J. Postembedding labeling on Lowicryl K4M tissue sections: detection and modification of cellular components. Methods Cell Biol. 1989;31:513–551. doi: 10.1016/s0091-679x(08)61625-8. [DOI] [PubMed] [Google Scholar]
- Russell D. W., Miller A. D. Foamy virus vectors. J Virol. 1996 Jan;70(1):217–222. doi: 10.1128/jvi.70.1.217-222.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Santillana-Hayat M., Rozain F., Bittoun P., Chopin-Robert C., Lasneret J., Périès J., Canivet M. Transient immunosuppressive effect induced in rabbits and mice by the human spumaretrovirus prototype HFV (human foamy virus). Res Virol. 1993 Sep-Oct;144(5):389–396. doi: 10.1016/s0923-2516(06)80054-3. [DOI] [PubMed] [Google Scholar]
- Saïb A., Koken M. H., van der Spek P., Périès J., de Thé H. Involvement of a spliced and defective human foamy virus in the establishment of chronic infection. J Virol. 1995 Sep;69(9):5261–5268. doi: 10.1128/jvi.69.9.5261-5268.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saïb A., Périès J., de Thé H. A defective human foamy provirus generated by pregenome splicing. EMBO J. 1993 Nov;12(11):4439–4444. doi: 10.1002/j.1460-2075.1993.tb06129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saïb A., Périès J., de Thé H. Recent insights into the biology of the human foamy virus. Trends Microbiol. 1995 May;3(5):173–178. doi: 10.1016/s0966-842x(00)88916-7. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Vale R. D. Intracellular transport using microtubule-based motors. Annu Rev Cell Biol. 1987;3:347–378. doi: 10.1146/annurev.cb.03.110187.002023. [DOI] [PubMed] [Google Scholar]
- Weiss R. A. Foamy retroviruses. A virus in search of a disease. Nature. 1988 Jun 9;333(6173):497–498. doi: 10.1038/333497a0. [DOI] [PubMed] [Google Scholar]
- Weiss R. A. Reverse transcription. Foamy viruses bubble on. Nature. 1996 Mar 21;380(6571):201–201. doi: 10.1038/380201a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Zack J. A., Arrigo S. J., Weitsman S. R., Go A. S., Haislip A., Chen I. S. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990 Apr 20;61(2):213–222. doi: 10.1016/0092-8674(90)90802-l. [DOI] [PubMed] [Google Scholar]
- Zack J. A., Haislip A. M., Krogstad P., Chen I. S. Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol. 1992 Mar;66(3):1717–1725. doi: 10.1128/jvi.66.3.1717-1725.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]