Virus nuclear membrane

Phosphorylate UL31 [ 87 ]. UL47 Alphaherpesvirinae Promote primary envelopment [ 78 ]. Not observed in PRV [ 88 , 89 ]. ICP22 Alphaherpesvirinae Promote primary envelopment [ 79 ]. Not observed in PRV [ 91 ]. UL51 Herpesviridae Promote de-envelopment [ 92 ]. Not observed in PRV [ 93 ]. Table 2 Cellular factors involved in nuclear egress of HSV capsids. Yes [ 6 ] p32 ICP Promote de-envelopment [ ]. Modulate fusion activity? Yes [ ]. Scission at the INM during Primary Envelopment Although NECs have the intrinsic capability to remodel membranes, they are unable to mediate primary envelopment by themselves in infected cells, as described above.

De-Envelopment 5. Overview of De-Envelopment De-envelopment is a process in which perinuclear virions fuse with the ONM to release naked capsids into the cytosol Figure 1 B.

Figure 3. Cellular Factors Involved in De-Envelopment In addition to viral factors, cellular factors also regulate the de-envelopment process Figure 3 and Table 2. Vesicle-Mediated Nucleocytoplasmic Transport in Uninfected Cells For a long time, vesicle-mediated nucleocytoplasmic transport was considered to be unique to the infection process used by herpesviruses.

Figure 4. Concluding Remarks Nuclear egress of viral capsids is essential during the life cycle of herpesviruses. Conflicts of Interest The author declares no conflict of interest. References 1. Hetzer M. The nuclear envelope. Cold Spring Harb. Crisp M. The nuclear envelope as an integrator of nuclear and cytoplasmic architecture. FEBS Lett.

Paci G. Cargo transport through the nuclear pore complex at a glance. Cell Sci. Hagen C. Johnson D. Herpesviruses remodel host membranes for virus egress. Speese S. Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling. Pellet P. In: Knipe D. Fields Virology.

Roizman B. Herpes simplex viruses. Schulz K. Herpesvirus nuclear egress: Pseudorabies Virus can simultaneously induce nuclear envelope breakdown and exit the nucleus via the envelopment-deenvelopment-pathway.

Virus Res. Leuzinger H. Herpes simplex virus 1 envelopment follows two diverse pathways. Wild P. Exploring the nuclear envelope of herpes simplex virus 1-infected cells by high-resolution microscopy. Mettenleiter T. Chang Y. The null mutant of the U L 31 gene of herpes simplex virus 1: Construction and phenotype in infected cells.

Roller R. Herpes simplex virus type 1 U L 34 gene product is required for viral envelopment. Klupp B. Primary envelopment of pseudorabies virus at the nuclear membrane requires the UL34 gene product. Fuchs W. The interacting UL31 and UL34 gene products of pseudorabies virus are involved in egress from the host-cell nucleus and represent components of primary enveloped but not mature virions.

Farina A. Popa M. Dominant negative mutants of the murine cytomegalovirus M53 gene block nuclear egress and inhibit capsid maturation. Shiba C. The UL34 gene product of herpes simplex virus type 2 is a tail-anchored type II membrane protein that is significant for virus envelopment.

Reynolds A. U L 31 and U L 34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids. Bigalke J. Structural basis of membrane budding by the nuclear egress complex of herpesviruses. EMBO J. Zeev-Ben-Mordehai T. Cell Rep. Lye M. Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex.

Leigh K. Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication. Walzer S. Gruenbaum Y. The nuclear lamina comes of age. Cell Biol. Muranyi W. Cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina. Scott E. Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection.

Conformational changes in the nuclear lamina induced by herpes simplex virus type 1 require genes U L 31 and U L Simpson-Holley M. Herpes simplex virus 1 U L 31 and U L 34 gene products promote the late maturation of viral replication compartments to the nuclear periphery. Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection.

Park R. Herpes simplex virus type 1 infection induces activation and recruitment of protein kinase C to the nuclear membrane and increased phosphorylation of lamin B. Bjerke S. Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress. Mou F.

Kuny C. Cyclin-dependent kinase-like function is shared by the beta- and gamma- subset of the conserved herpesvirus protein kinases. PLoS Pathog. Lee C. Epstein-Barr virus BGLF4 kinase induces disassembly of the nuclear lamina to facilitate virion production. Hamirally S. Leach N. Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3.

Morris J. Herpes simplex virus infection induces phosphorylation and delocalization of emerin, a key inner nuclear membrane protein.

Wang Y. Turan A. Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1. Full F. Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity.

Schreiber K. When lamins go bad: Nuclear structure and disease. Silva L. Role for A-type lamins in herpesviral DNA targeting and heterochromatin modulation. Roles of the nuclear lamina in stable nuclear association and assembly of a herpesviral transactivator complex on viral immediate-early genes. Analysis of a charge cluster mutation of herpes simplex virus type 1 UL34 and its extragenic suppressor suggests a novel interaction between pUL34 and pUL31 that is necessary for membrane curvature around capsids.

Funk C. Trus B. Sheaffer A. Herpes simplex virus DNA cleavage and packaging proteins associate with the procapsid prior to its maturation. Thurlow J. The herpes simplex virus type 1 DNA packaging protein UL17 is a virion protein that is present in both the capsid and the tegument compartments. Newcomb W. Herpes simplex virus capsid structure: DNA packaging protein UL25 is located on the external surface of the capsid near the vertices.

Yang K. Association of herpes simplex virus pUL31 with capsid vertices and components of the capsid vertex-specific complex.

Takeshima K. Draganova E. Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress. Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins. Luitweiler E. Desai P. Membrane deformation and scission by the HSV-1 nuclear egress complex. Lorenz M. A single herpesvirus protein can mediate vesicle formation in the nuclear envelope.

Arii J. Thaller D. Roussel E. Naldinho-Souto R. Herpes simplex virus tegument protein VP16 is a component of primary enveloped virions. Bucks M. Donnelly M. Pomeranz L. Modified VP22 localizes to the cell nucleus during synchronized herpes simplex virus type 1 infection.

Henaff D. Analysis of the early steps of herpes simplex virus 1 capsid tegumentation. Luxton G. Leelawong M. Nuclear egress of pseudorabies virus capsids is enhanced by a subspecies of the large tegument protein that is lost upon cytoplasmic maturation. Huet A. Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery. Cardone G.

TEM analysis revealed that, in the absence of capsids, NEC aggregates correspond to multi-folded nuclear membrane structures, suggesting that pUS3 may control NEC self-association and membrane deformation. To determine the significance of the pUS3 nuclear egress function for virus growth, the replication of single and double UL34 and US3 mutants was measured, showing that the significance of pUS3 nuclear egress function is cell-type specific.

Importance The nuclear lamina is an important player in infection by viruses that replicate in the nucleus. Herpesviruses alter the structure of the nuclear lamina to facilitate transport of capsids from the nucleus to the cytoplasm and use both viral and cellular effectors to disrupt the protein-protein interactions that maintain the lamina. It has been speculated that the presence of virions in these punctate nuclear membrane extensions for simplicity of discussion, here termed NM evaginations reflects a delay in egress from the perinuclear space Klupp et al.

Interestingly, NM evaginations do not occur in cells infected with viruses bearing mutations that obviate U L 34 phosphorylation by U S 3. The identity of these novel substrate s is of considerable interest, and U L 31 is a lead candidate to explain the effects of U S 3 on virion envelopment at the INM.

The localization of gK at the ultrastructural level has yet to be determined, largely because few epitopes in this mostly hydrophobic protein are recognized by available antibodies. In monolayers of tightly packed Vero cells infected with a U L 53 deletion mutant, nucleocapsids accumulate in the nucleus and few are detected in the cytoplasm, suggesting that at least under some conditions, gK plays an important role in nucleocapsid envelopment at the INM Jayachandra et al.

How the protein facilitates nucleocapsid envelopment is not known. The U L 11 protein, composed of residues, is both myristoylated and palmitoylated Loomis et al. Both modifications contribute to the association with membranes whereas an acidic cluster mediates trafficking from the plasma membrane to the Golgi apparatus in uninfected cells Loomis et al.

Cells infected with the U L 11 deletion virus produce infectious virus at levels —fold below those of wild-type viruses Baines and Roizman, The most striking abnormalities in cells infected with this mutant are abundant unenveloped nucleocapsids in the cytoplasm and abutting the INM. These observations suggest roles in nucleocapsid envelopment at the nuclear membrane or completion of the envelopment reaction, and a second defect in cytoplasmic egress.

The latter could reflect a defect that causes de-envelopment or one that precludes re-envelopment at cytoplasmic membranes. Although the U L 11 protein is targeted to the INM and cytoplasmic membranes of infected cells, the protein localizes primarily to the Golgi apparatus in uninfected cells Baines et al.

The disparity between localization in infected and uninfected cells suggests that other infected cell proteins, or alteration of membranes or membrane trafficking by HSV helps mediate trafficking of the U L 11 protein to the nuclear membrane.

Unlike many tegument proteins, the low U L 37 protein copy number in the virion tegument is invariant McLaughlin, , suggesting that it binds a repetitive structure on the nucleocapsid, and might serve as a limiting factor for tegument formation. A likely repetitive feature of nucleocapsids, and possible binding point of UL37 protein, would include capsid pentons which are structurally distinct from hexons and are believed to serve as anchor points for the tegument Zhou et al.

In pseudorabies virus, the ortholog of U L 37 has been termed a primary tegument protein to indicate its presence in the tegument layer most intimately assocated with the surface of the nucleocapsid Mettenleiter, Deletion of U L 37 does not greatly affect production of nucleocapsides, but causes most of these to remain in the nucleus at time after infection when large amounts of cytoplasmic particles would be expected Desai et al. Thus U L 37 is ultimately dispensable for nucleocapsid envelopment, but greatly facilitates the process.

Taken together, the data suggest the perhaps oversimplified hypothesis that U L 37 protein association with intranuclear capsids serves to bridge the nucleocapsid to a U L interacting protein in the envelopment apparatus at the INM, but how pU L 37 becomes incorporated into the tegument, or whether it interacts with appropriate envelopment proteins to accomplish a bridging function have yet to be determined. A model for nucleocapsid envelopment at the nuclear membrane that is consistent with the above data is as follows.

The protein migrates past the nuclear pore complex and into the INM where it engages U L 31 protein located in the lamina, causing it to become anchored in the INM. These regions also contain the U L 31 and U L 34 protein complex. The U L 31 and U L 34 proteins are left at the ONM, and the de-enveloped nucleocapsid proceeds into the cytoplasm to receive another membrane from a cytoplasmic organelle.

Although the above model is consistent with current observations, it is likely that certain aspects and future surprises will invite revision as more data accumulates. The usefulness of the model lies in its many testable predictions, and it is hoped that such a paradigm will invite vigorous experimentation in the future. Turn recording back on.

National Center for Biotechnology Information , U. Search database Search term. Cambridge: Cambridge University Press ; Search term. Chapter 11 Envelopment of herpes simplex virus nucleocapsids at the inner nuclear membrane Joel D. Author Information Authors Joel D. Introduction As in all herpesviruses, Herpes simplex nucleocapsids assembled in the nucleoplasm obtain an initial envelope by budding through the inner nuclear membrane of infected cells. Envelopment at the nuclear membrane Herpesvirus nucleocapsids are unique in virology because their nucleocapsids bud through the inner nuclear membrane INM to obtain a virion envelope.

Budding from the nuclear membrane A promininent hypothesis is that the U L 31 and U L 34 proteins are retained at the inner nuclear membrane to engage nucleocapsids during envelopment. U L 11 The U L 11 protein, composed of residues, is both myristoylated and palmitoylated Loomis et al.

U L 37 Unlike many tegument proteins, the low U L 37 protein copy number in the virion tegument is invariant McLaughlin, , suggesting that it binds a repetitive structure on the nucleocapsid, and might serve as a limiting factor for tegument formation. Model of nucleocapsid envelopment at the INM A model for nucleocapsid envelopment at the nuclear membrane that is consistent with the above data is as follows.

References Baines J. The U L 11 gene of herpes simplex virus 1 encodes a function that facilitates nucleocapsid envelopment and egress from cells.

Baines J. The U L 20 gene of herpes simplex virus 1 encodes a function necessary for viral egress. The U L 11 gene products of herpes simplex virus 1 are present in the nuclear and cytoplasmic membranes, and intranuclear dense bodies of infected cells. Belmont A. Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. Cell Biol. Bjerke S.

Effects of charged cluster mutations on the function of herpes simplex virus type 1 UL34 protein. Chang Y. The product of the U L 31 gene of herpes simplex virus 1 is a nuclear phosphoprotein which partitions with the nuclear matrix.

The null mutant of the U L 31 gene of herpes simplex virus 1: construction and phenotype of infected cells. Clements L. Direct interaction between emerin and lamin A.

Desai P. A null mutation in the gene encoding the herpes simplex virus type 1 UL37 polypeptide abrogates virus maturation. Dhe-Paganon S. Structure of the globular tail of nuclear lamin. Ellenberg J. Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis.

Fisher D. Natl Acad. Gonnella R. Gruenbaum Y. Hoger T. Amino acid sequence and molecular characterization of murine lamin B as deduced from cDNA clones. Characterization of a second highly conserved B-type lamin present in cells previously thought to contain only a single B-type lamin. Izumi M. Jayachandra S.