Cyclophilin A incorporation is not required for human immunodeficiency virus type 1 particle maturation and does not destabilize the mature capsid - PubMed (original) (raw)
. 1999 Apr 25;257(1):261-74.
doi: 10.1006/viro.1999.9669.
Affiliations
- PMID: 10208939
- DOI: 10.1006/viro.1999.9669
Free article
Cyclophilin A incorporation is not required for human immunodeficiency virus type 1 particle maturation and does not destabilize the mature capsid
K Wiegers et al. Virology. 1999.
Free article
Abstract
The cellular protein cyclophilin A (CypA) is packaged into human immunodeficiency virus type 1 (HIV-1) virions through a specific interaction with the capsid (CA) domain of the Gag polyprotein. CypA is important for infectivity, but its role in viral replication is currently unknown. Previous reports suggested that CypA promotes uncoating or enhances maturation. We analyzed the morphology and capsid stability of HIV-1 variants defective in CypA binding and of virus grown in the presence of cyclosporin. Both cyclosporin treatment and alteration of Gly89 or Pro90 in the CypA-binding site of CA caused a 5- to 20-fold decrease in CypA incorporation. Virus produced from cyclosporin-treated cells and variants G89V and G89A were 10- to 100-fold less infectious but exhibited normal virion morphologies with regular cone-shaped capsids. Irregular capsid morphologies and lower infectivities were observed for some other variants in the CypA-binding region. Decreased CypA incorporation did not reduce the kinetics of intracellular polyprotein processing or of virus release. No increase in immature particles was observed. These results suggest that CypA does not promote virion maturation. Furthermore, detergent stripping of virus particles with various CypA contents revealed no difference in capsid stability. Based on these results and those reported in the accompanying paper, it appears likely that CypA also is not an uncoating factor. Alternative models for CypA function are discussed.
Copyright 1999 Academic Press.
Similar articles
- In vitro assembly properties of wild-type and cyclophilin-binding defective human immunodeficiency virus capsid proteins in the presence and absence of cyclophilin A.
Grättinger M, Hohenberg H, Thomas D, Wilk T, Müller B, Kräusslich HG. Grättinger M, et al. Virology. 1999 Apr 25;257(1):247-60. doi: 10.1006/viro.1999.9668. Virology. 1999. PMID: 10208938 - Proline residues in the HIV-1 NH2-terminal capsid domain: structure determinants for proper core assembly and subsequent steps of early replication.
Fitzon T, Leschonsky B, Bieler K, Paulus C, Schröder J, Wolf H, Wagner R. Fitzon T, et al. Virology. 2000 Mar 15;268(2):294-307. doi: 10.1006/viro.1999.0178. Virology. 2000. PMID: 10704338 - Specific incorporation of cyclophilin A into HIV-1 virions.
Franke EK, Yuan HE, Luban J. Franke EK, et al. Nature. 1994 Nov 24;372(6504):359-62. doi: 10.1038/372359a0. Nature. 1994. PMID: 7969494 - The molecular architecture of HIV.
Briggs JA, Kräusslich HG. Briggs JA, et al. J Mol Biol. 2011 Jul 22;410(4):491-500. doi: 10.1016/j.jmb.2011.04.021. J Mol Biol. 2011. PMID: 21762795 Review. - [The structure and virus-like particle vaccine of the HIV-1 capsid protein].
Sun XG, Song CZ. Sun XG, et al. Sheng Wu Gong Cheng Xue Bao. 2003 Sep;19(5):516-20. Sheng Wu Gong Cheng Xue Bao. 2003. PMID: 15969076 Review. Chinese.
Cited by
- Functional surfaces of the human immunodeficiency virus type 1 capsid protein.
von Schwedler UK, Stray KM, Garrus JE, Sundquist WI. von Schwedler UK, et al. J Virol. 2003 May;77(9):5439-50. doi: 10.1128/jvi.77.9.5439-5450.2003. J Virol. 2003. PMID: 12692245 Free PMC article. - Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection.
Luban J. Luban J. J Virol. 2007 Feb;81(3):1054-61. doi: 10.1128/JVI.01519-06. Epub 2006 Sep 6. J Virol. 2007. PMID: 16956947 Free PMC article. Review. No abstract available. - Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2.
Kane M, Rebensburg SV, Takata MA, Zang TM, Yamashita M, Kvaratskhelia M, Bieniasz PD. Kane M, et al. Elife. 2018 Aug 7;7:e35738. doi: 10.7554/eLife.35738. Elife. 2018. PMID: 30084827 Free PMC article. - Redistribution of cyclophilin A to viral factories during vaccinia virus infection and its incorporation into mature particles.
Castro AP, Carvalho TM, Moussatché N, Damaso CR. Castro AP, et al. J Virol. 2003 Aug;77(16):9052-68. doi: 10.1128/jvi.77.16.9052-9068.2003. J Virol. 2003. PMID: 12885921 Free PMC article. - CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A.
Pushkarsky T, Zybarth G, Dubrovsky L, Yurchenko V, Tang H, Guo H, Toole B, Sherry B, Bukrinsky M. Pushkarsky T, et al. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6360-5. doi: 10.1073/pnas.111583198. Epub 2001 May 15. Proc Natl Acad Sci U S A. 2001. PMID: 11353871 Free PMC article.