Biochemical and Structural Analysis of Isolated Mature Cores of Human Immunodeficiency Virus Type 1

Welker, Reinhold; Hohenberg, Heinz; Tessmer, Uwe; Huckhagel, Carola; Kräusslich, Hans‐Georg

doi:10.1128/jvi.74.3.1168-1177.2000

Cited by 186 publications

(217 citation statements)

References 61 publications

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“…Fullerene cones require twelve pentameric declinations ("pentons") to close and can adopt one of five allowed cone angles. The narrowest allowed cone angle (19.2°) predominates in both authentic HIV-1 capsids and in "synthetic" capsids assembled from pure recombinant proteins [89,93,96]. These narrow cones are closed by inclusion of five and seven pentons at their narrow and wide ends, respectively (Fig.…”

Section: Mature Retroviral Capsids Are Fullerene Structuresmentioning

confidence: 98%

The structural biology of HIV assembly

Ganser‐Pornillos

Yeager

Sundquist

2008

Current Opinion in Structural Biology

406

422

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HIV assembly and replication proceed through formation of morphologically distinct immature and mature viral capsids that are organized by the Gag polyprotein (immature) and by the fully processed CA protein (mature). The Gag polyprotein is composed of three folded polypeptides (MA, CA, and NC) and three smaller peptides (SP1, SP2, and p6) that function together to coordinate membrane binding and Gag-Gag lattice interactions in immature virions. Following budding, HIV maturation is initiated by proteolytic processing of Gag, which induces conformational changes in the CA domain and results in assembly of the distinctive conical capsid. Retroviral capsids are organized following the principles of fullerene cones, and the hexagonal CA lattice is stabilized by three distinct interfaces. Recently identified inhibitors of viral maturation act by disrupting the final stage of Gag processing, or by inhibiting formation of a critical intermolecular CA-CA interface in the mature capsid. Following release into a new host cell, the capsid disassembles and host cell factors can potently restrict this stage of retroviral replication. Here, we review the structures of immature and mature HIV virions, focusing on recent studies that have defined the global organization of the immature Gag lattice, identified sites likely to undergo conformational changes during maturation, revealed the molecular structure of the mature capsid lattice, demonstrated that capsid architectures are conserved, identified the first capsid assembly inhibitors, and begun to uncover the remarkable biology of the mature capsid.

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Section: Mature Retroviral Capsids Are Fullerene Structuresmentioning

confidence: 98%

The structural biology of HIV assembly

Ganser‐Pornillos

Yeager

Sundquist

2008

Current Opinion in Structural Biology

406

422

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“…25,30 We performed Immunogold staining on paraformaldehyde-fixed sections of PDHs using corespecific and L-specific antisera as described. 30 We acquired and processed the images using DigitalMicrograph (Gatan).…”

Section: Electron Microscopymentioning

confidence: 99%

Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles

et al. 2007

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Formation of enveloped viruses involves assembly and budding at cellular membranes. In this study, we elucidated the morphogenesis of hepadnaviruses on the ultrastructural and biochemical level using duck hepatitis B virus (DHBV) as a model system. Formation of virus progeny initiates at the endoplasmic reticulum (ER) and is conserved both in vitro and in vivo. The morphogenesis proceeds via membrane-surrounded vesicles containing both virions and subviral particles, indicating a common morphogenetic pathway. The virus particle-containing vesicles (VCVs) are generated and maintained by reorganization of endomembranes accompanied by a striking disorganization of the rough ER (rER). DHBV-infected hepatocytes produce not only complete virions, but also large quantities of subviral particles (SVPs). SVPs are devoid of the nucleocapsid and viral DNA, 4,5 but contain the envelope proteins. The extracellular DHB virion has a spherical structure of approximately 45 to 65 nm and contains an electron-dense nucleocapsid of about 27 nm. 6 Little is known about the morphogenesis of this virus family, but several of the following features indicate that this process is likely to be unique and complex: the DHB viral envelope proteins are multispanning transmembrane proteins, encoded by a single open reading frame, whose differential transcription results in the large (L) and the small (S) surface protein. 7 Both proteins share an identical carboxyterminal region, representing the S protein, with an additional Nterminal extension forming the preS-region of L. The ratio between the L and S proteins in the viral particles is about 1:4. 8 As the major structural component of the envelope, the S protein determines envelope curvature and is indispensable for both budding and secretion of viral particles. 9 Both surface proteins are synthesized at the rough endoplasmic reticulum (ER), or rER, and then bud into the ER lumen, forming SVPs. This budding event is autonomous and independent of all other viral components (e.g., nucleocapsid). 10,11 The intrinsic membrane-deforming activity of hepadnaviral envelope proteins is host cell-independent and conserved from yeast to

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“…A recent study on the primer binding site of the equine infectious anemia virus has shown that the hairpin present in that region induces a strong pause of reverse transcription that increases the efficiency of the docking step (15). In addition, in vitro studies on the effect on strand transfer of the nucleocapsid protein (NC), a major co-factor of the reverse transcription complex (19), have suggested a mechanism of recombination governed by the structures of the RNA rather than by pausing of reverse transcription (reviewed in Refs. 3 and 20).…”

mentioning

confidence: 99%

Evidence for a Mechanism of Recombination during Reverse Transcription Dependent on the Structure of the Acceptor RNA

Moumen

Polomack

Unge

et al. 2003

Journal of Biological Chemistry

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Genetic recombination is a major force driving retroviral evolution. In retroviruses, recombination proceeds mostly through copy choice during reverse transcription. Using a reconstituted in vitro system, we have studied the mechanism of strand transfer on a major recombination hot spot we previously identified within the genome of HIV-1. We show that on this model sequence the frequency of copy choice is strongly influenced by the folding of the RNA template, namely by the presence of a stable hairpin. This structure must be specifically present on the acceptor template. We previously proposed that strand transfer follows a two-step process: docking of the nascent DNA onto the acceptor RNA and strand invasion. The frequency of recombination under copy choice conditions was not dependent on the concentration of the acceptor RNA, in contrast with strand transfer occurring at strong arrests of reverse transcription. During copy choice strand transfer, the docking step is not rate limiting. We propose that the hairpin present on the acceptor RNA could mediate strand transfer following a mechanism reminiscent of branch migration during DNA recombination.

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Biochemical and Structural Analysis of Isolated Mature Cores of Human Immunodeficiency Virus Type 1

Cited by 186 publications

References 61 publications

The structural biology of HIV assembly

The structural biology of HIV assembly

Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles

Evidence for a Mechanism of Recombination during Reverse Transcription Dependent on the Structure of the Acceptor RNA

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