Abstract
LITTLE is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl–prolyl isomerases1; cyclophilins catalyse a rate-limiting step in protein folding2 and protect cells from heat shock3. Here we demonstrate that cyclophilin A is specifically incorporated into HIV-1 virions but not into virions of other primate immunodeficiency viruses. A proline-rich region conserved in all HIV-1 Gag polyproteins is required for cyclophilin A binding and incorporation. Disruption of a single proline blocks the Gag–cyclophilin interactionin vitro, prevents cyclophilin A incorporation into virions, and inhibits H1V-1 replication. Our results indicate that the interaction of Gag with cyclophilin A is necessary for the formation of infectious HIV-1 virions.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Luban, J., Bossolt, K. A., Franke, E. K., Kalpana, G. V. & Goff, S. P. Cell 73, 1067–1078 (1993).
Fischer, G. & Schmid, F. X. Biochemistry 29, 2205–2212 (1990).
Sykes, K., Gething, M.-J. & Sambrook, J. Proc. natn. Acad. Sci. U.S.A. 90, 5853–5857 (1993).
Hasel, K. W., Glass, J. R., Godbout, M. & Sutcliffe, J. G. Molec. cell. Biol. 11, 3484–3491 (1991).
Panet, A., Baltimore, D. & Hanafusa, T. J. Virol. 16, 146–152 (1975).
Myers, G., Wain-Hobson, S., Korber, B., Smith, R. F. & Pavlakis, G. N. Human Retroviruses and AIDS (Los Alamos National Laboratory, Los Alamos, 1993).
Koletsky, A. J., Harding, M. W. & Handschumacher, R. E. J. Immun. 137, 1054–1059 (1986).
Rosenwirth, B. et al. Antimicro. Agents Chemother. 38, 1763–1772 (1994).
Karpas, A., Lowdell, M., Jacobson, S. & Hill, F. Proc. natn. Acad. Sci. U.S.A. 89, 8351–8355 (1992).
Luban, J. & Goff, S. J. Virol. 65, 3203–3212 (1991).
Franke, E. K., Yuan, H. E.-H., Bossolt, K. L., Goff, S. P. & Luban, J. J. Virol. 68, 5300–5305 (1994).
Jin, M. J. et al. EMBO J. 13, 2935–2947 (1994).
Friedman, J. & Weissman, I. Cell 66, 799–806 (1991).
Liu, J. et al. Cell 66, 807–815 (1991).
Adachi, A. et al. J. Virol. 59, 284–291 (1986).
Dewhurst, S., Embretson, J. E., Anderson, D. C., Mullins, J. I. & Fultz, P. N. Nature 345, 636–640 (1990).
Guyader, M. et al. Nature 326, 662–669 (1987).
Kestler, H. et al. Science 248, 1109–1112 (1990).
Kornfeld, H., Riedel, N., Viglianti, G. A., Hirsch, V. & Mullins, J. I. Nature 326, 610–613 (1987).
Bram, R. J., Hung, D. T., Martin, P. K., Schreiber, S. L. & Crabtree, G. Molec cell. Biol. 13, 4760–4769 (1993).
Schwartz, S. et al. J. Virol. 66, 7176–7182 (1992).
Cullen, B. Meth. Enzym. 152, 684–704 (1987).
Luban, J. & Goff, S. P. J. Virol. 68, 3784–3793 (1994).
Paxton, W., Connor, R. I. & Landau, N. R. J. Virol. 67, 7229–7237 (1993).
Field, J. et al. Molec cell. Biol. 8, 2159–2165 (1988).
Mammano, F., Ohagen, A., Hoglund, S. & Gottlinger, H. G. J. Virol. 68, 4927–4936 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Franke, E., Yuan, H. & Luban, J. Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372, 359–362 (1994). https://doi.org/10.1038/372359a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/372359a0
This article is cited by
-
Primate TRIM34 is a broadly-acting, TRIM5-dependent lentiviral restriction factor
Retrovirology (2023)
-
HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules
Retrovirology (2021)
-
Arginyl-tRNA-protein transferase 1 contributes to governing optimal stability of the human immunodeficiency virus type 1 core
Retrovirology (2021)
-
Cyclophilin A protects HIV-1 from restriction by human TRIM5α
Nature Microbiology (2019)
-
Shielding the HIV-1 capsid
Nature Microbiology (2019)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.