HIV-1 and MLV Gag proteins are sufficient to recruit APOBEC3G into virus-like particles

Douaisi, Marc; Dussart, Sylvie; Courcoul, Marianne; Bessou, Gilles; Vigne, Robert; Decroly, Étienne

doi:10.1016/j.bbrc.2004.07.005

Cited by 90 publications

(75 citation statements)

References 21 publications

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“…It is relevant that the C terminus of HTLV-1 NC contributes to the exclusion of hA3G from VLPs, because it is NC that brings viral and cellular RNAs into the virion. It is currently believed that both NC and RNA are necessary for incorporation of hA3G into virions (19,20,22,(32)(33)(34), but it is unclear whether hA3G is simply tethered to RNA (21,22,34) or interacts with a NC-RNA complex (11). Deleting 20 aa near the C terminus of HTLV-1 NC (NCDC mutant) did not alter the amount of viral RNA in virions but did increase the amount of hA3G that was packaged.…”

Section: Discussionmentioning

confidence: 99%

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Derse

Hill

Princler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

113

118

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Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes in vivo, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing an accessory protein, Vif, which hastens the degradation of hA3G. In contrast, HTLV-1 does not encode a Vif homologue; instead, HTLV-1 has evolved a cis-acting mechanism to prevent hA3G restriction. We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction. Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins.

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Section: Discussionmentioning

confidence: 99%

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Derse

Hill

Princler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

113

118

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“…Virus infectivity factor facilitates polyubiquitination of Apo3G, resulting in proteasomal degradation (2)(3)(4)(5)(6). When virus infectivity factor is absent, however, Apo3G is encapsulated in the HIV virus particle, most likely as a multimer (7), through interactions with HIV RNA or 7SL RNA and the nucleocapsid portion of Gag (7)(8)(9)(10)(11)(12)(13)(14)(15). Following release from the HIV virion into T cells, Apo3G generates large numbers of deaminations, typically 5Ј-CCC3 CCU, in viral (Ϫ) single-stranded cDNA during reverse transcription (16 -18).…”

mentioning

confidence: 99%

Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G

Chelico

Prochnow

Erie

et al. 2010

Journal of Biological Chemistry

108

244

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APOBEC3G (Apo3G) is a single-stranded DNA-dependent deoxycytidine deaminase, which, in the absence of the human immunodeficiency virus (HIV) viral infectivity factor, is encapsulated into HIV virions. Subsequently, Apo3G triggers viral inactivation by processively deaminating C3 U, with 335 polarity, on nascent minus-strand cDNA. Apo3G has a catalytically inactive N-terminal CD1 domain and an active C-terminal CD2 domain. Apo3G exists as monomers, dimers, tetramers, and higher order oligomers whose distributions depend on DNA substrate and salt. Here we use multiangle light scattering and atomic force microscopy to identify oligomerization states of Apo3G. A double mutant (F126A/W127A), designed to disrupt dimerization at the predicted CD1-CD1 dimer interface, predominantly converts Apo3G to a monomer that binds singlestranded DNA, Alu RNA, and catalyzes processive C3 U deaminations with 335 deamination polarity, similar to native Apo3G. The CD1 domain is essential for both processivity and polarity. We propose a structure-based model to explain the scanning and catalytic behavior of Apo3G.

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“…The HIV-1 Gag protein is responsible for facilitating APOBEC3G incorporation into virions as evidenced by the fact that Gag virus-like particles (VLPs) efficiently incorporate APOBEC3G (10,31,38). Furthermore, in vitro binding experiments have shown that APOBEC3G binds efficiently to the nucleocapsid (NC) region of the Gag polyprotein (1,4,19,26,31,38).…”

mentioning

confidence: 99%

APOBEC3G Multimers Are Recruited to the Plasma Membrane for Packaging into Human Immunodeficiency Virus Type 1 Virus-Like Particles in an RNA-Dependent Process Requiring the NC Basic Linker

Burnett

Spearman

2007

J Virol

102

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APOBEC3G is an endogenous host restriction factor that inhibits human immunodeficiency virus (HIV)replication. The antiviral activity of APOBEC3G is dependent upon its incorporation into the virus particle. The mechanisms governing incorporation of APOBEC3G into virus particles are not completely understood. In particular, some investigators have reported that APOBEC3G interacts directly with the nucleocapsid (NC) subunit of Gag, while others have found that an RNA intermediate is required for Gag-APOBEC3G interactions. In this study, we confirmed the RNA dependence of APOBEC3G packaging and performed detailed mapping of the determinants within NC that are required for virion incorporation. Surprisingly, APOBEC3G packaging did not correlate well with the presence of the N-terminal "I," or interaction, domain within NC. Specifically, Gag constructs containing only the N-terminal region of NC packaged minimal amounts of APOBEC3G, while significant levels of APOBEC3G packaging were achieved with Gag constructs containing the basic linker region of NC. Furthermore, membrane-binding experiments revealed that the basic linker region was essential for the membrane association of APOBEC3G in a Gag-APOBEC3G complex. Fluorescence resonance energy transfer was detected between labeled APOBEC3G in cells and in particles, indicating that APOBEC3G is packaged as a multimer that is bound to packaged RNA. Regions of APOBEC3G-Gag colocalization at the plasma membrane were detected that were distinct from the punctate cytoplasmic bodies where APOBEC3G accumulates within the cell. Together, our results indicate that APOBEC3G multimerizes in an RNA-dependent fashion and that RNA-APOBEC3G multimers are recruited to the plasma membrane and subsequently into virion particles by Gag.

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HIV-1 and MLV Gag proteins are sufficient to recruit APOBEC3G into virus-like particles

Cited by 90 publications

References 21 publications

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G

APOBEC3G Multimers Are Recruited to the Plasma Membrane for Packaging into Human Immunodeficiency Virus Type 1 Virus-Like Particles in an RNA-Dependent Process Requiring the NC Basic Linker

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