Strain-specific Differences in the Impact of Human TRIM5alpha, Different TRIM5alpha Alleles, and the Inhibition of Capsid-cyclophilin A Interactions on the Infectivity of HIV-1

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2010 Aug 13

PMID 20702630

Citations 27

Authors

Emilie Battivelli

Denise Lecossier

Saori Matsuoka

Julie Migraine

Francois Clavel

Allan J Hance

Affiliations

Soon will be listed here.

Abstract

HIV-1 infectivity is strongly restricted by TRIM5α from certain primate species but has been described as being only marginally susceptible to human TRIM5α. In this study, we evaluated the effects of the modulation of human TRIM5α activity (pretreatment of target cells with alpha interferon, expression of a pre-miRNA targeting TRIM5α, and/or overexpression of TRIM5γ), the inhibition of cyclophilin A (CypA)-CA interactions, and the expression of different allelic variants of human TRIM5α on the infectivity of a series of recombinant viruses carrying different patient-derived Gag-protease sequences. We show that HIV-1 displays virus-specific differences in its sensitivity to human TRIM5α and in its sensitivity to different TRIM5α alleles. The effect of inhibiting CypA-CA interactions is also strain specific, and blocking these interactions can either inhibit or improve viral infectivity, depending on the isolate studied. The inhibition of CypA-CA interactions also modulates viral sensitivity to human TRIM5α. In the absence of CypA-CA interactions, most viruses displayed increased sensitivity to the inhibitory effects of TRIM5α on viral replication, but one isolate showed a paradoxical decrease in sensitivity to TRIM5α. Taken together, these findings support a model in which three interlinked factors--capsid sequence, CypA levels, and TRIM5α--interact to determine capsid stability and therefore viral infectivity.

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References

Mische C, Javanbakht H, Song B, Diaz-Griffero F, Stremlau M, Strack B . Retroviral restriction factor TRIM5alpha is a trimer. J Virol. 2005; 79(22):14446-50. PMC: 1280198. DOI: 10.1128/JVI.79.22.14446-14450.2005. View

Zhang F, Hatziioannou T, Perez-Caballero D, Derse D, Bieniasz P . Antiretroviral potential of human tripartite motif-5 and related proteins. Virology. 2006; 353(2):396-409. DOI: 10.1016/j.virol.2006.05.035. View

Owens C, Song B, Perron M, Yang P, Stremlau M, Sodroski J . Binding and susceptibility to postentry restriction factors in monkey cells are specified by distinct regions of the human immunodeficiency virus type 1 capsid. J Virol. 2004; 78(10):5423-37. PMC: 400345. DOI: 10.1128/jvi.78.10.5423-5437.2004. View

Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H . Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci U S A. 2006; 103(14):5514-9. PMC: 1459386. DOI: 10.1073/pnas.0509996103. View

Towers G, Hatziioannou T, Cowan S, Goff S, Luban J, Bieniasz P . Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nat Med. 2003; 9(9):1138-43. DOI: 10.1038/nm910. View

Towers G . The control of viral infection by tripartite motif proteins and cyclophilin A. Retrovirology. 2007; 4:40. PMC: 1906832. DOI: 10.1186/1742-4690-4-40. View

Price A, Marzetta F, Lammers M, Ylinen L, Schaller T, Wilson S . Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Nat Struct Mol Biol. 2009; 16(10):1036-42. PMC: 3556581. DOI: 10.1038/nsmb.1667. View

Javanbakht H, Diaz-Griffero F, Stremlau M, Si Z, Sodroski J . The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5alpha. J Biol Chem. 2005; 280(29):26933-40. DOI: 10.1074/jbc.M502145200. View

Stremlau M, Song B, Javanbakht H, Perron M, Sodroski J . Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1. Virology. 2006; 351(1):112-20. DOI: 10.1016/j.virol.2006.03.015. View

10.

Thomas D, Voronin Y, Nikolenko G, Chen J, Hu W, Pathak V . Determination of the ex vivo rates of human immunodeficiency virus type 1 reverse transcription by using novel strand-specific amplification analysis. J Virol. 2007; 81(9):4798-807. PMC: 1900155. DOI: 10.1128/JVI.02471-06. View

11.

Sokolskaja E, Berthoux L, Luban J . Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus type 1 infectivity in human cells. J Virol. 2006; 80(6):2855-62. PMC: 1395419. DOI: 10.1128/JVI.80.6.2855-2862.2006. View

12.

Aberham C, Weber S, Phares W . Spontaneous mutations in the human immunodeficiency virus type 1 gag gene that affect viral replication in the presence of cyclosporins. J Virol. 1996; 70(6):3536-44. PMC: 190228. DOI: 10.1128/JVI.70.6.3536-3544.1996. View

13.

Gamble T, Vajdos F, Yoo S, Worthylake D, Houseweart M, Sundquist W . Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell. 1996; 87(7):1285-94. DOI: 10.1016/s0092-8674(00)81823-1. View

14.

Berthoux L, Sebastian S, Sokolskaja E, Luban J . Cyclophilin A is required for TRIM5{alpha}-mediated resistance to HIV-1 in Old World monkey cells. Proc Natl Acad Sci U S A. 2005; 102(41):14849-53. PMC: 1239943. DOI: 10.1073/pnas.0505659102. View

15.

Sakuma R, Mael A, Ikeda Y . Alpha interferon enhances TRIM5alpha-mediated antiviral activities in human and rhesus monkey cells. J Virol. 2007; 81(18):10201-6. PMC: 2045407. DOI: 10.1128/JVI.00419-07. View

16.

Kootstra N, Navis M, Beugeling C, van Dort K, Schuitemaker H . The presence of the Trim5alpha escape mutation H87Q in the capsid of late stage HIV-1 variants is preceded by a prolonged asymptomatic infection phase. AIDS. 2007; 21(15):2015-23. DOI: 10.1097/QAD.0b013e3282effa87. View

17.

Fitzon T, Leschonsky B, Bieler K, Paulus C, Schroder J, Wolf H . Proline residues in the HIV-1 NH2-terminal capsid domain: structure determinants for proper core assembly and subsequent steps of early replication. Virology. 2000; 268(2):294-307. DOI: 10.1006/viro.1999.0178. View

18.

Forshey B, von Schwedler U, Sundquist W, Aiken C . Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication. J Virol. 2002; 76(11):5667-77. PMC: 137032. DOI: 10.1128/jvi.76.11.5667-5677.2002. View

19.

Goldschmidt V, Bleiber G, May M, Martinez R, Ortiz M, Telenti A . Role of common human TRIM5alpha variants in HIV-1 disease progression. Retrovirology. 2006; 3:54. PMC: 1560158. DOI: 10.1186/1742-4690-3-54. View

20.

Li S, Hill C, Sundquist W, Finch J . Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature. 2000; 407(6802):409-13. DOI: 10.1038/35030177. View