1887

Abstract

We characterized a persistently Junín virus (JUNV)-infected BHK-21 cell line obtained by experimental infection with the XJCl3 strain. This cell line, named K3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (DI) particles after the first year of infection. K3 cells were able to exclude superinfection of the homologous JUNV and the antigenically related Tacaribe virus (TCRV), whereas the non-related arenaviruses lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV) could replicate normally. Although superinfecting virus binding and internalization to persistently infected cells were slightly reduced, earlier biosynthesis of antigenomic RNA was observed in comparison with BHK-21 cells. Despite the fact that superinfection did not increase the number of cells expressing viral antigens, de novo synthesis of superinfecting virus proteins was detected. The virus produced by JUNV-superinfected K3 cells remained mostly cell-associated in the form of particles tethered to the plasma membrane and aberrant tubular structures. JUNV restriction was correlated with an overexpression of cellular protein TSG101 in K3 cells, which has been pointed out as involved in the budding of several RNA viruses. This correlation was also observed in a cell clone isolated from K3. Reduction of TSG101 expression favoured the release of infectious virus to the supernatant of JUNV-superinfected K3 cells. Our data suggest that overexpression of TSG101 in K3 cells is a novel mechanism that may contribute, along with a diminished synthesis of superinfecting virus proteins, to explain superinfection exclusion in persistently arenavirus-infected cells.

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2007-10-01
2024-04-20
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References

  1. Amit I., Yakir L., Katz M., Zwang Y., Marmor M. D., Citri A., Shtiegman K., Alroy I., Tuvia S. other authors 2004; Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding. Genes Dev 18:1737–1752 [CrossRef]
    [Google Scholar]
  2. Auperin D. D., Romanowski V., Galinski M., Bishop D. H. 1984; Sequencing studies of Pichinde arenavirus S RNA indicate a novel coding strategy, an ambisense viral S RNA. J Virol 52:897–904
    [Google Scholar]
  3. Babst M., Odorizzi G., Estepa E. J., Emr S. D. 2000; Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic 1:248–258 [CrossRef]
    [Google Scholar]
  4. Bouamr F., Melillo J. A., Wang M. Q., Nagashima K., de Los Santos M., Rein A., Goff S. P. 2003; PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101. J Virol 77:11882–11895 [CrossRef]
    [Google Scholar]
  5. Buchmeier M. J. 2002; Arenaviruses: protein structure and function. Curr Top Microbiol Immunol 262:159–173
    [Google Scholar]
  6. Castilla V., Mersich S. E. 1996; Low-pH-induced fusion of Vero cells infected with Junín virus. Arch Virol 141:1307–1317 [CrossRef]
    [Google Scholar]
  7. Castilla V., Barquero A. A., Mersich S. E., Coto C. E. 1998; In vitro anti-Junín virus activity of a peptide isolated from Melia azedarach L. leaves. Int J Antimicrob Agents 10:67–75 [CrossRef]
    [Google Scholar]
  8. Christen L., Seto J., Niles E. G. 1990; Superinfection exclusion of vaccinia virus in virus-infected cell cultures. Virology 174:35–42 [CrossRef]
    [Google Scholar]
  9. Cornu T. I., de la Torre J. C. 2001; RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome. J Virol 75:9415–9426 [CrossRef]
    [Google Scholar]
  10. D'Aiutolo A. C., Coto C. E. 1986; Vero cells persistently infected with Tacaribe virus: role of interfering particles in the establishment of the infection. Virus Res 6:235–244 [CrossRef]
    [Google Scholar]
  11. Damonte E. B., Mersich S. E., Coto C. E. 1983; Response of cells persistently infected with arenaviruses to superinfection with homotypic and heterotypic viruses. Virology 129:474–478 [CrossRef]
    [Google Scholar]
  12. Damonte E. B., Mersich S. E., Candurra N. A. 1994; Intracellular processing and transport of Junín virus glycoproteins influences virion infectivity. Virus Res 34:317–326 [CrossRef]
    [Google Scholar]
  13. Demirov D. G., Ono A., Orenstein J. M., Freed E. O. 2002; Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function. Proc Natl Acad Sci U S A 99:955–960 [CrossRef]
    [Google Scholar]
  14. Ellenberg P., Edreira M., Lozano M., Scolaro L. 2002; Synthesis and expression of viral antigens in Vero cells persistently infected with Junín virus. Arch Virol 147:1543–1557 [CrossRef]
    [Google Scholar]
  15. Ellenberg P., Edreira M., Scolaro L. 2004; Resistance to superinfection of Vero cells persistently infected with Junín virus. Arch Virol 149:507–522 [CrossRef]
    [Google Scholar]
  16. Garcin D., Rochat S., Kolakofsky D. 1993; The Tacaribe arenavirus small zinc finger protein is required for both mRNA synthesis and genome replication. J Virol 67:807–812
    [Google Scholar]
  17. Garrus J. E., von Schwedler U. K., Pornillos O. W., Morham S. G., Zavitz K. H., Wang H. E., Wettstein D. A., Stray K. M., Cote M. other authors 2001; Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107:55–65 [CrossRef]
    [Google Scholar]
  18. Goila-Gaur R., Demirov D. G., Orenstein J. M., Ono A., Freed E. O. 2003; Defects in human immunodeficiency virus budding and endosomal sorting induced by TSG101 overexpression. J Virol 77:6507–6519 [CrossRef]
    [Google Scholar]
  19. Harty R. N., Brown M. E., Wang G., Huibregtse J., Hayes F. P. 2000; A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. Proc Natl Acad Sci U S A 97:13871–13876 [CrossRef]
    [Google Scholar]
  20. Iapalucci S., Chernavsky A., Rossi C., Burgin M. J., Franze-Fernandez M. T. 1994; Tacaribe virus gene expression in cytopathic and non-cytopathic infections. Virology 200:613–622 [CrossRef]
    [Google Scholar]
  21. Irie T., Licata J. M., McGettigan J. P., Schnell M. J., Harty R. N. 2004; Budding of PPxY-containing rhabdoviruses is not dependent on host proteins TGS101 and VPS4A. J Virol 78:2657–2665 [CrossRef]
    [Google Scholar]
  22. Jacamo R., Lopez N., Wilda M., Franze-Fernandez M. T. 2003; Tacaribe virus Z protein interacts with the L polymerase protein to inhibit viral RNA synthesis. J Virol 77:10383–10393 [CrossRef]
    [Google Scholar]
  23. Karpf A. R., Lenches E., Strauss E. G., Strauss J. H., Brown D. T. 1997; Superinfection exclusion of alphaviruses in three mosquito cell lines persistently infected with Sindbis virus. J Virol 71:7119–7123
    [Google Scholar]
  24. Lee K. J., Novella I. S., Teng M. N., Oldstone M. B., de La Torre J. C. 2000; NP and L proteins of lymphocytic choriomeningitis virus (LCMV) are sufficient for efficient transcription and replication of LCMV genomic RNA analogs. J Virol 74:3470–3477 [CrossRef]
    [Google Scholar]
  25. Lopez N., Jacamo R., Franze-Fernandez M. T. 2001; Transcription and RNA replication of Tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes. J Virol 75:12241–12251 [CrossRef]
    [Google Scholar]
  26. Lu Q., Hope L. W., Brasch M., Reinhard C., Cohen S. N. 2003; TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. Proc Natl Acad Sci U S A 100:7626–7631 [CrossRef]
    [Google Scholar]
  27. Ludlow M., McQuaid S., Cosby S. L., Cattaneo R., Rima B. K., Duprex W. P. 2005; Measles virus superinfection immunity and receptor redistribution in persistently infected NT2 cells. J Gen Virol 86:2291–2303 [CrossRef]
    [Google Scholar]
  28. Meyer B. J., de la Torre J. C., Southern P. J. 2002; Arenaviruses: genomic RNAs, transcription, and replication. Curr Top Microbiol Immunol 262:139–157
    [Google Scholar]
  29. Michel N., Allespach I., Venzke S., Fackler O. T., Keppler O. T. 2005; The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4. Curr Biol 15:714–723 [CrossRef]
    [Google Scholar]
  30. Perez M., Craven R. C., de la Torre J. C. 2003; The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A 100:12978–12983 [CrossRef]
    [Google Scholar]
  31. Radoshitzky S. R., Abraham J., Spiropoulou C. F., Kuhn J. H., Nguyen D., Li W., Nagel J., Schmidt P. J., Nunberg J. H. other authors 2007; Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446:92–96 [CrossRef]
    [Google Scholar]
  32. Rima B. K., Duprex W. P. 2005; Molecular mechanisms of measles virus persistence. Virus Res 111:132–147 [CrossRef]
    [Google Scholar]
  33. Salvato M., Shimomaye E., Oldstone M. B. 1989; The primary structure of the lymphocytic choriomeningitis virus L gene encodes a putative RNA polymerase. Virology 169:377–384 [CrossRef]
    [Google Scholar]
  34. Sanchez A., Pifat D. Y., Kenyon R. H., Peters C. J., McCormick J. B., Kiley M. P. 1989; Junín virus monoclonal antibodies: characterization and cross-reactivity with other arenaviruses. J Gen Virol 70:1125–1132 [CrossRef]
    [Google Scholar]
  35. Strecker T., Eichler R., Meulen J., Weissenhorn W., Dieter Klenk H., Garten W., Lenz O. 2003; Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles. J Virol 77:10700–10705 [CrossRef]
    [Google Scholar]
  36. Tortorici M. A., Albarino C. G., Posik D. M., Ghiringhelli P. D., Lozano M. E., Rivera Pomar R., Romanowski V. 2001; Arenavirus nucleocapsid protein displays a transcriptional antitermination activity in vivo. Virus Res 73:41–55 [CrossRef]
    [Google Scholar]
  37. Urata S., Noda T., Kawaoka Y., Yokosawa H., Yasuda J. 2006; Cellular factors required for Lassa virus budding. J Virol 80:4191–4195 [CrossRef]
    [Google Scholar]
  38. Whitaker-Dowling P., Youngner J. S., Widnell C. C., Wilcox D. K. 1983; Superinfection exclusion by vesicular stomatitis virus. Virology 131:137–143 [CrossRef]
    [Google Scholar]
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