This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yin, L.
Right arrow Articles by Luban, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yin, L.
Right arrow Articles by Luban, J.

 Previous Article  |  Next Article 

J Virol, August 1998, p. 6430-6436, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Replication Is Modulated by Host Cyclophilin A Expression Levels

Lei Yin,1 Douglas Braaten,1 and Jeremy Luban1,2,*

Departments of Microbiology1 and Medicine,2 Columbia University, College of Physicians and Surgeons, New York, New York 10032

Received 19 November 1997/Accepted 25 April 1998

Human immunodeficiency virus type 1 (HIV-1) Gag and the cellular protein cyclophilin A form an essential complex in the virion core: virions produced by proviruses encoding Gag mutants with decreased cyclophilin A affinity exhibit attenuated infectivity, as do virions produced in the presence of the competitive inhibitor cyclosporine. The A224E Gag mutant has no effect on cyclophilin A affinity but renders HIV-1 replication cyclosporine resistant in Jurkat T cells. In contrast, A224E mutant virus is dead in H9 T cells, although replication is rescued by cyclosporine or by expression in cis of a Gag mutant that decreases cyclophilin A-affinity. The observation that disruption of the Gag-cyclophilin A interaction rescues A224E mutant replication in H9 cells prompted experiments which revealed that, relative to Jurkat cells, H9 cells express greater quantities of cyclophilin A. The resulting larger quantity of cyclophilin A shown to be packaged into virions produced by H9 cells is presumably disruptive to the A224E mutant virion core. Further evidence that increased cyclophilin A expression in H9 cells is of functional relevance was provided by the finding that Gag mutants with decreased cyclophilin A affinity are dead in Jurkat cells but capable of replication in H9 cells. Similarly, cyclosporine concentrations which inhibit wild-type HIV-1 replication in Jurkat cells stimulate HIV-1 replication in H9 cells. These results suggest that HIV-1 virion infectivity imposes narrow constraints upon cyclophilin A stoichiometry in virions and that infectivity is finely tuned by host cyclophilin A expression levels.

* Corresponding author. Mailing address: Departments of Microbiology and Medicine, Columbia University, College of Physicians and Surgeons, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8706. Fax: (212) 305-0333. E-mail: Luban{at}cuccfa.ccc.columbia.edu.

J Virol, August 1998, p. 6430-6436, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Li, Y., Kar, A. K., Sodroski, J. (2009). Target Cell Type-Dependent Modulation of Human Immunodeficiency Virus Type 1 Capsid Disassembly by Cyclophilin A. J. Virol. 83: 10951-10962 [Abstract] [Full Text]  
  • Arfi, V., Lienard, J., Nguyen, X.-N., Berger, G., Rigal, D., Darlix, J.-L., Cimarelli, A. (2009). Characterization of the Behavior of Functional Viral Genomes during the Early Steps of Human Immunodeficiency Virus Type 1 Infection. J. Virol. 83: 7524-7535 [Abstract] [Full Text]  
  • Ylinen, L. M. J., Schaller, T., Price, A., Fletcher, A. J., Noursadeghi, M., James, L. C., Towers, G. J. (2009). Cyclophilin A Levels Dictate Infection Efficiency of Human Immunodeficiency Virus Type 1 Capsid Escape Mutants A92E and G94D. J. Virol. 83: 2044-2047 [Abstract] [Full Text]  
  • Qi, M., Yang, R., Aiken, C. (2008). Cyclophilin A-Dependent Restriction of Human Immunodeficiency Virus Type 1 Capsid Mutants for Infection of Nondividing Cells. J. Virol. 82: 12001-12008 [Abstract] [Full Text]  
  • Ptak, R. G., Gallay, P. A., Jochmans, D., Halestrap, A. P., Ruegg, U. T., Pallansch, L. A., Bobardt, M. D., de Bethune, M.-P., Neyts, J., De Clercq, E., Dumont, J.-M., Scalfaro, P., Besseghir, K., Wenger, R. M., Rosenwirth, B. (2008). Inhibition of Human Immunodeficiency Virus Type 1 Replication in Human Cells by Debio-025, a Novel Cyclophilin Binding Agent. Antimicrob. Agents Chemother. 52: 1302-1317 [Abstract] [Full Text]  
  • Brockman, M. A., Schneidewind, A., Lahaie, M., Schmidt, A., Miura, T., DeSouza, I., Ryvkin, F., Derdeyn, C. A., Allen, S., Hunter, E., Mulenga, J., Goepfert, P. A., Walker, B. D., Allen, T. M. (2007). Escape and Compensation from Early HLA-B57-Mediated Cytotoxic T-Lymphocyte Pressure on Human Immunodeficiency Virus Type 1 Gag Alter Capsid Interactions with Cyclophilin A. J. Virol. 81: 12608-12618 [Abstract] [Full Text]  
  • Song, C., Aiken, C. (2007). Analysis of Human Cell Heterokaryons Demonstrates that Target Cell Restriction of Cyclosporine-Resistant Human Immunodeficiency Virus Type 1 Mutants Is Genetically Dominant. J. Virol. 81: 11946-11956 [Abstract] [Full Text]  
  • Yang, R., Aiken, C. (2007). A Mutation in Alpha Helix 3 of CA Renders Human Immunodeficiency Virus Type 1 Cyclosporin A Resistant and Dependent: Rescue by a Second-Site Substitution in a Distal Region of CA. J. Virol. 81: 3749-3756 [Abstract] [Full Text]  
  • Saini, M., Potash, M. J. (2006). Novel Activities of Cyclophilin A and Cyclosporin A during HIV-1 Infection of Primary Lymphocytes and Macrophages. J. Immunol. 177: 443-449 [Abstract] [Full Text]  
  • Keckesova, Z., Ylinen, L. M. J., Towers, G. J. (2006). Cyclophilin A Renders Human Immunodeficiency Virus Type 1 Sensitive to Old World Monkey but Not Human TRIM5{alpha} Antiviral Activity.. J. Virol. 80: 4683-4690 [Abstract] [Full Text]  
  • Sokolskaja, E., Berthoux, L., Luban, J. (2006). Cyclophilin A and TRIM5{alpha} Independently Regulate Human Immunodeficiency Virus Type 1 Infectivity in Human Cells. J. Virol. 80: 2855-2862 [Abstract] [Full Text]  
  • Gatanaga, H., Das, D., Suzuki, Y., Yeh, D. D., Hussain, K. A., Ghosh, A. K., Mitsuya, H. (2006). Altered HIV-1 Gag Protein Interactions with Cyclophilin A (CypA) on the Acquisition of H219Q and H219P Substitutions in the CypA Binding Loop. J. Biol. Chem. 281: 1241-1250 [Abstract] [Full Text]  
  • Chatterji, U., Bobardt, M. D., Stanfield, R., Ptak, R. G., Pallansch, L. A., Ward, P. A., Jones, M. J., Stoddart, C. A., Scalfaro, P., Dumont, J.-M., Besseghir, K., Rosenwirth, B., Gallay, P. A. (2005). Naturally Occurring Capsid Substitutions Render HIV-1 Cyclophilin A Independent in Human Cells and TRIM-cyclophilin-resistant in Owl Monkey Cells. J. Biol. Chem. 280: 40293-40300 [Abstract] [Full Text]  
  • Cantin, R., Methot, S., Tremblay, M. J. (2005). Plunder and Stowaways: Incorporation of Cellular Proteins by Enveloped Viruses. J. Virol. 79: 6577-6587 [Full Text]  
  • Hatziioannou, T., Perez-Caballero, D., Cowan, S., Bieniasz, P. D. (2005). Cyclophilin Interactions with Incoming Human Immunodeficiency Virus Type 1 Capsids with Opposing Effects on Infectivity in Human Cells. J. Virol. 79: 176-183 [Abstract] [Full Text]  
  • Sokolskaja, E., Sayah, D. M., Luban, J. (2004). Target Cell Cyclophilin A Modulates Human Immunodeficiency Virus Type 1 Infectivity. J. Virol. 78: 12800-12808 [Abstract] [Full Text]  
  • Berthoux, L., Sebastian, S., Sokolskaja, E., Luban, J. (2004). Lv1 Inhibition of Human Immunodeficiency Virus Type 1 Is Counteracted by Factors That Stimulate Synthesis or Nuclear Translocation of Viral cDNA. J. Virol. 78: 11739-11750 [Abstract] [Full Text]  
  • Ikeda, Y., Ylinen, L. M. J., Kahar-Bador, M., Towers, G. J. (2004). Influence of gag on Human Immunodeficiency Virus Type 1 Species-Specific Tropism. J. Virol. 78: 11816-11822 [Abstract] [Full Text]  
  • Liu, S., Asparuhova, M., Brondani, V., Ziekau, I., Klimkait, T., Schumperli, D. (2004). Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting cyclophilin A. Nucleic Acids Res 32: 3752-3759 [Abstract] [Full Text]  
  • Ganser-Pornillos, B. K., von Schwedler, U. K., Stray, K. M., Aiken, C., Sundquist, W. I. (2004). Assembly Properties of the Human Immunodeficiency Virus Type 1 CA Protein. J. Virol. 78: 2545-2552 [Abstract] [Full Text]  
  • Kootstra, N. A., Munk, C., Tonnu, N., Landau, N. R., Verma, I. M. (2003). Abrogation of postentry restriction of HIV-1-based lentiviral vector transduction in simian cells. Proc. Natl. Acad. Sci. USA 100: 1298-1303 [Abstract] [Full Text]  
  • Roy, J., Paquette, J.-S., Fortin, J.-F., Tremblay, M. J. (2002). The Immunosuppressant Rapamycin Represses Human Immunodeficiency Virus Type 1 Replication. Antimicrob. Agents Chemother. 46: 3447-3455 [Abstract] [Full Text]  
  • Bosco, D. A., Eisenmesser, E. Z., Pochapsky, S., Sundquist, W. I., Kern, D. (2002). Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proc. Natl. Acad. Sci. USA 99: 5247-5252 [Abstract] [Full Text]  
  • Fujita, M., Yoshida, A., Miyaura, M., Sakurai, A., Akari, H., Koyama, A. H., Adachi, A. (2001). Cyclophilin A-Independent Replication of a Human Immunodeficiency Virus Type 1 Isolate Carrying a Small Portion of the Simian Immunodeficiency Virus SIVMAC gag Capsid Region. J. Virol. 75: 10527-10531 [Abstract] [Full Text]  
  • Dietrich, L., Ehrlich, L. S., LaGrassa, T. J., Ebbets-Reed, D., Carter, C. (2001). Structural Consequences of Cyclophilin A Binding on Maturational Refolding in Human Immunodeficiency Virus Type 1 Capsid Protein. J. Virol. 75: 4721-4733 [Abstract] [Full Text]  
  • Öhagen, A., Gabuzda, D. (2000). Role of Vif in Stability of the Human Immunodeficiency Virus Type 1 Core. J. Virol. 74: 11055-11066 [Abstract] [Full Text]  
  • Mouland, A. J., Mercier, J., Luo, M., Bernier, L., DesGroseillers, L., Cohen, E. A. (2000). The Double-Stranded RNA-Binding Protein Staufen Is Incorporated in Human Immunodeficiency Virus Type 1: Evidence for a Role in Genomic RNA Encapsidation. J. Virol. 74: 5441-5451 [Abstract] [Full Text]  
  • Burniston, M. T., Cimarelli, A., Colgan, J., Curtis, S. P., Luban, J. (1999). Human Immunodeficiency Virus Type 1 Gag Polyprotein Multimerization Requires the Nucleocapsid Domain and RNA and Is Promoted by the Capsid-Dimer Interface and the Basic Region of Matrix Protein. J. Virol. 73: 8527-8540 [Abstract] [Full Text]  
  • Cartier, C., Sivard, P., Tranchat, C., Decimo, D., Desgranges, C., Boyer, V. (1999). Identification of Three Major Phosphorylation Sites within HIV-1 Capsid. ROLE OF PHOSPHORYLATION DURING THE EARLY STEPS OF INFECTION. J. Biol. Chem. 274: 19434-19440 [Abstract] [Full Text]  
  • Bosco, D. A., Eisenmesser, E. Z., Pochapsky, S., Sundquist, W. I., Kern, D. (2002). Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proc. Natl. Acad. Sci. USA 99: 5247-5252 [Abstract] [Full Text]  
  • Pushkarsky, T., Zybarth, G., Dubrovsky, L., Yurchenko, V., Tang, H., Guo, H., Toole, B., Sherry, B., Bukrinsky, M. (2001). CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc. Natl. Acad. Sci. USA 98: 6360-6365 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»