Fragmentation and dispersal of Golgi proteins and redistribution of glycoproteins and glycolipids processed through the Golgi apparatus after infection with herpes simplex virus 1.

Campadelli, G.; Brandimarti, Renato; Lazzaro, C.; Ward, P L; Roizman, Bernard; Torrisi, Maria Rosaria

doi:10.1073/pnas.90.7.2798

Cited by 123 publications

(97 citation statements)

References 31 publications

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“…4 A and B). At this later point in infection, the TGN was largely dispersed, in line with previous reports (17,27,28). By 15-40 min after washout, extensive Tyr-MT networks had reformed.…”

Section: Hsv-1 Induces Mt Reorganization and Stabilization In Primarysupporting

confidence: 76%

“…Our findings demonstrate that in the absence of a centrosome, the TGN acts as an alternate MTOC in HSV-1-infected cells, with MTs emanating from the TGN rapidly becoming acetylated. MTs have been described as "disorganized" and seemingly originating from multiple locations, rather than a singular site, during HSV-1 infection (17,24,27). The dispersed nature of the TGN and its ability to act as an MTOC in infected cells, illustrated here, offers an explanation for these previous observations.…”

Section: Discussionmentioning

confidence: 50%

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Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread

Naghavi

Gundersen

Walsh

2013

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

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Although microtubules (MTs) frequently form highly dynamic networks, subsets of MTs become stabilized in response to environmental cues and function as specialized tracks for vesicle and macromolecular trafficking. MT stabilization is controlled by specialized plus-end tracking proteins (+TIPs) whose accumulation at the MT ends is facilitated by the end-binding protein, EB1, and regulated by various signaling pathways. As cargoes themselves, viruses are dependent on MTs for their intracellular movement. Although many viruses affect MT organization, the potential contribution of MT stabilization by +TIPs to infection remains unknown. Here we show that early in infection of primary human fibroblasts, herpes simplex virus type 1 (HSV-1) disrupts the centrosome, the primary MT organizing center in many cell types. As infection progresses HSV-1 induces the formation of stable MT subsets through inactivation of glycogen synthase kinase 3beta by the viral Ser/Thr kinase, Us3. Stable MT formation is reduced in cells infected with Us3 mutants and those stable MTs that form cluster around the trans-Golgi network. Downstream of glycogen synthase kinase 3beta, cytoplasmic linker-associated proteins (CLASPs), specialized host +TIPs that control MT formation at the trans-Golgi network and cortical capture, are specifically required for virus-induced MT stabilization and HSV-1 spread. Our findings demonstrate the biological importance of +TIPs to viral infection and suggest that HSV-1 has evolved to exploit the trans-Golgi network as an alternate MT organizing center to facilitate virus spread.M icrotubules (MTs) function in a variety of processes, including directed intracellular trafficking of cargos and changes in cell shape, polarity, and motility (1, 2). Consisting of polarized heteropolymers of α/β-tubulin, in most cells MT minusends are anchored at the perinuclear MT organizing center (MTOC), whereas their plus-ends radiate toward the cell periphery. In proliferating cells, the majority of MTs are highly dynamic, growing and shrinking through the addition or loss of tubulin subunits primarily at the plus-end. Dynamic instability facilitates intracellular sensing through "search-and-capture." On encountering targets such as the cell cortex and in response to specific signals, subsets of MTs become stabilized and acquire posttranslational modifications such as acetylation and detyrosination (3). Stable MTs are recognized by specific motor proteins and act as specialized tracks for vesicle transport (1, 3). MT stabilization is mediated by proteins that track dynamic MT plusends and influence rates of MT growth, pause, and collapse, known as plus-end tracking proteins (+TIPs) (4). Central to plusend tracking is EB1, a member of the end-binding family of proteins that recognizes growing MT ends. Although many +TIPs are capable of associating with MTs, it is their interaction with EB1 that mediates their specific accumulation at MT plus-ends (4). +TIP activity and interaction with EB1 responds to signals including Rho-Dia act...

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“…4 A and B). At this later point in infection, the TGN was largely dispersed, in line with previous reports (17,27,28). By 15-40 min after washout, extensive Tyr-MT networks had reformed.…”

Section: Hsv-1 Induces Mt Reorganization and Stabilization In Primarysupporting

confidence: 76%

Section: Discussionmentioning

confidence: 50%

Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread

Naghavi

Gundersen

Walsh

2013

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

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“…However, only microtubules showed some bundling, which was detected 2 h after fragmentation of membranes had been completed. Fragmentation and dispersal of the Golgi complex has also been observed during infection with herpes simplex virus in different cell types (7). This effect, mediated at least partly by fragmentation of microtubules, has been described as a late event caused by the huge influx of viral glycoproteins contained in virions and membranes flowing through the exocytic pathway.…”

Section: Discussionmentioning

confidence: 91%

Polymorphism and Structural Maturation of Bunyamwera Virus in Golgi and Post-Golgi Compartments

Salanueva

Novoa

Cabezas

et al. 2003

J Virol

118

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The Golgi apparatus is the assembly site for a number of complex enveloped viruses. Using high-preservation methods for electron microscopy, we have detected two previously unknown maturation steps in the morphogenesis of Bunyamwera virus in BHK-21 cells. The first maturation takes place inside the Golgi stack, where annular immature particles transform into dense, compact structures. Megalomicin, a drug that disrupts the trans side of the Golgi complex, reversibly blocks transformation, showing that a functional trans-Golgi is needed for maturation. The second structural change seems to take place during the egress of viral particles from cells, when a coat of round-shaped spikes becomes evident. A fourth viral assembly was detected in infected cells: rigid tubular structures assemble in the Golgi region early in infection and frequently connect with mitochondria. In Vero cells, the virus induces an early and spectacular fragmentation of intracellular membranes while productive infection progresses. Assembly occurs in fragmented Golgi stacks and generates tubular structures, as well as the three spherical viral forms. These results, together with our previous studies with nonrelated viruses, show that the Golgi complex contains key factors for the structural transformation of a number of enveloped viruses that assemble intracellularly.

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“…One model, developed for HSV-1, proposes a single budding event of nucleocapsids at the inner leaflet of the nuclear membrane, followed by virion transport inside vesicles through the secretory pathway to the Golgi complex and exocytosis at the cell surface (6,7,11,24,47). Another model proposes deenvelopment of virions during transit through the outer leaflet of the perinuclear membrane and a secondary envelopment step in the trans-Golgi region.…”

Section: Discussionmentioning

confidence: 99%

Egress of Alphaherpesviruses: Comparative Ultrastructural Study

Granzow¹,

Klupp

Fuchs

et al. 2001

J Virol

242

241

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Egress of four important alphaherpesviruses, equine herpesvirus 1 (EHV-1), herpes simplex virus type 1 (HSV-1), infectious laryngotracheitis virus (ILTV), and pseudorabies virus (PrV), was investigated by electron microscopy of infected cell lines of different origins. In all virus-cell systems analyzed, similar observations were made concerning the different stages of virion morphogenesis. After intranuclear assembly, nucleocapsids bud at the inner leaflet of the nuclear membrane, resulting in enveloped particles in the perinuclear space that contain a sharply bordered rim of tegument and a smooth envelope surface. Egress from the perinuclear cisterna primarily occurs by fusion of the primary envelope with the outer leaflet of the nuclear membrane, which has been visualized for HSV-1 and EHV-1 for the first time. The resulting intracytoplasmic naked nucleocapsids are enveloped at membranes of the trans-Golgi network (TGN), as shown by immunogold labeling with a TGN-specific antiserum. Virions containing their final envelope differ in morphology from particles within the perinuclear cisterna by visible surface projections and a diffuse tegument. Particularly striking was the addition of a large amount of tegument material to ILTV capsids in the cytoplasm. Extracellular virions were morphologically identical to virions within Golgi-derived vesicles, but distinct from virions in the perinuclear space. Studies with gB-and gH-deleted PrV mutants indicated that these two glycoproteins, which are essential for virus entry and direct cell-to-cell spread, are dispensable for egress. Taken together, our studies indicate that the deenvelopment-reenvelopment process of herpesvirus maturation also occurs in EHV-1, HSV-1, and ILTV and that membrane fusion processes occurring during egress are substantially different from those during entry and direct viral cell-to-cell spread.Herpesviruses are large DNA-containing enveloped viruses that replicate in the nuclei of infected cells. Based on biological parameters and sequence data, the family Herpesviridae is divided into the subfamilies Alpha-, Beta-, and Gammaherpesvirinae (58). Despite their biological diversity, many steps of herpesvirus morphogenesis seem to be conserved. Attached herpesvirus virions penetrate the cell membrane by direct fusion between the viral envelope and the plasma membrane, and the deenveloped nucleocapsids reach the nucleopores by movement along cellular microtubuli, where the genomic DNA is released into the nucleus (19,50,51,52). Progeny nucleocapsids assemble in the nucleus and exit this compartment by budding at the inner nuclear membrane into the perinuclear space (35,47). The subsequent events of envelopment and egress remain controversial. Whereas for herpes simplex virus type 1 (HSV-1), a model that entails vesicular transport of enveloped virions through the secretory pathway with concomitant in situ modification of virion glycoproteins was initially proposed, for varicella-zoster virus (VZV), pseudorabies virus (PrV), and human cytomegalovir...

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Fragmentation and dispersal of Golgi proteins and redistribution of glycoproteins and glycolipids processed through the Golgi apparatus after infection with herpes simplex virus 1.

Cited by 123 publications

References 31 publications

Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread

Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread

Polymorphism and Structural Maturation of Bunyamwera Virus in Golgi and Post-Golgi Compartments

Egress of Alphaherpesviruses: Comparative Ultrastructural Study

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