Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins

Klupp, Barbara G.; Granzow, Harald; Fuchs, Walter; Keil, Günther M.; Finke, Stefan; Mettenleiter, Thomas

doi:10.1240/sav_gbm_2007_m_001665

Cited by 9 publications

(16 citation statements)

References 14 publications

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“…Moreover, additional NEC activities were demonstrated in studies on nuclear membrane vesicles, which could be induced through coexpression of herpesviral pUL50 and pUL53 homologs in the absence of virus infection . Intriguingly, Bigalke et al recently demonstrated that the purified core NEC of HSV‐1 is sufficient for membrane budding in vitro .…”

Section: Resultsmentioning

confidence: 99%

The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids

Marschall

Muller²,

Diewald³

et al. 2017

Reviews in Medical Virology

114

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Current evidence refined the view about herpesviral NECs. Datasets published for HCMV, murine CMV, herpes simplex virus, and Epstein-Barr virus illustrate the marked functional consistency in the way herpesviruses achieve nuclear egress. However, this compares with only limited sequence conservation of core NEC proteins and a structural conservation restricted to individual domains. The translational use of this information might help to define a novel antiviral strategy on the basis of NEC-directed small molecules.

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Section: Resultsmentioning

confidence: 99%

The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids

Marschall

Muller²,

Diewald³

et al. 2017

Reviews in Medical Virology

114

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“…Two viral proteins, pUL31 and pUL34, structurally and functionally conserved in the Herpesviridae , form a complex and are required to soften and at least partially dissolve the nuclear lamina for the nucleocapsid to achieve the intimate contact with the INM (reviewed by Mettenleiter et al, 2006). The coexpression of these two proteins from PRV has been shown to be sufficient to induce the formation of vesicles from the nuclear membrane (Klupp et al, 2007). Homologues of both proteins in two gammaherpesviruses, EBV (BFLF2 and BFRF1) (Gonnella et al, 2005) and KSHV (ORF69 and ORF67) (Santarelli et al, 2008), have also been reported to be involved in primary envelopment processes.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Visualization of Gammaherpesvirus Life Cycle in Host Cells by Electron Tomography

Ryazantsev

Sun

et al. 2010

Structure

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Summary Gammaherpesviruses are etiologically associated with human tumors. A three-dimensional (3D) examination of their life cycle in the host is lacking, significantly limiting our understanding of the structural and molecular basis of virus-host interactions. Here, we report the first 3D visualization of key stages of the murine gammaherpesvirus 68 life cycle in NIH3T3 cells, including viral attachment, entry, assembly and egress, by dual-axis electron tomography. In particular, we revealed the transient processes of incoming capsids injecting viral DNA through nuclear pore complexes and nascent DNA being packaged into progeny capsids in vivo as a spool coaxial with the putative portal vertex. We discovered that intranuclear invagination of both nuclear membranes is involved in nuclear egress of herpesvirus capsids. Taken together, our results provide the structural basis for a detailed mechanistic description of gammaherpesvirus life cycle and also demonstrate the advantage of electron tomography in dissecting complex cellular processes of viral infection.

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“…In the absence of either UL31 or UL34, viral replication is impaired and most capsids are retained in the nucleus (Roller et al , ; Fuchs et al , ). The NEC is also sufficient to drive the vesiculation of the nuclear envelope in transfected cells in the absence of any other viral proteins (Klupp et al , ; Desai et al , ; Luitweiler et al , ). These results demonstrated that UL31 and UL34 are the only viral proteins necessary for nuclear envelope vesiculation but left the exact function of the NEC in membrane budding unclear.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of membrane budding by the nuclear egress complex of herpesviruses

2015

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During nuclear egress, herpesvirus capsids bud at the inner nuclear membrane forming perinuclear viral particles that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytoplasm. This unusual budding process is mediated by the nuclear egress complex (NEC) composed of two conserved viral proteins, UL31 and UL34. Earlier, we discovered that the herpesvirus nuclear egress complex (NEC) could bud synthetic membranes in vitro without the help of other proteins by forming a coat-like hexagonal scaffold inside the budding membrane. To understand the structural basis of NEC-mediated membrane budding, we determined the crystal structures of the NEC from two herpesviruses. The hexagonal lattice observed in the NEC crystals recapitulates the honeycomb coats within the budded vesicles. Perturbation of the oligomeric interfaces through mutagenesis blocks budding in vitro confirming that NEC oligomerization into a honeycomb lattice drives budding. The structure represents the first atomic-level view of an oligomeric array formed by a membrane-deforming protein, making possible the dissection of its unique budding mechanism and the design of inhibitors to block it.

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Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins

Cited by 9 publications

References 14 publications

The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids

The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids

Three-Dimensional Visualization of Gammaherpesvirus Life Cycle in Host Cells by Electron Tomography

Structural basis of membrane budding by the nuclear egress complex of herpesviruses

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