Genetic Analysis of the Role of Herpes Simplex Virus Type 1 Glycoprotein K in Infectious Virus Production and Egress

Foster, Timothy P.; Kousoulas, Konstantin G.

doi:10.1128/jvi.73.10.8457-8468.1999

Cited by 85 publications

(30 citation statements)

References 48 publications

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“…HSV-1 carries at least 85 genes, which are divided into two groups based on whether they are essential for virus replication in vitro (28). Both the gK and UL20 genes are considered essential genes for HSV-1 replication in vitro and in vivo (2)(3)(4)(29)(30)(31)(32). We have reported previously that immunization of mice with HSV-1 gK exacerbates eye disease in ocularly infected mice (33,34) and that recombinant viruses expressing two additional copies of HSV-1 gK exacerbate eye disease in ocularly infected mice (25).…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of the roles of UL20 and its regulation in vivo are hampered by the essential role of UL20 and the inability of UL20 deletion mutants of HSV-1 to replicate efficiently in vitro or in vivo (3,4,32). Our recent construction of GODZ Ϫ/Ϫ mice (19), however, enabled investigation of the contribution of the GODZ component of the UL20-gK network to HSV-1 infectivity using MEFs derived from these mice, as well as in vivo analysis.…”

Section: Discussionmentioning

confidence: 99%

“…T he herpes simplex virus 1 (HSV-1)-encoded protein UL20 is essential for cytoplasmic envelopment of virions and virus egress. UL20 has been shown to interact with HSV-1 glycoprotein K (gK) (1), and both UL20 and gK are classified as essential genes for HSV-1 infectivity (1)(2)(3)(4)(5). We found recently that UL20 binds to GODZ (Golgi-specific DHHC zinc finger protein)/DHHC3, a member of the Asp-His-His-Cys (DHHC) family of palmitoyl transferases (6).…”

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confidence: 99%

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The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection

Wang¹,

Mott²,

Cilluffo³

et al. 2018

J Virol

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UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 () gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20. HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity and viral pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection

Wang¹,

Mott²,

Cilluffo³

et al. 2018

J Virol

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“…Whereas HSV-1 gK had so far only been detected in the endoplasmic reticulum and nuclear membranes of infected cells (14), it has been found in virions of PrV and VZV (25,32). Detailed studies of HSV-1, PrV, and VZV demonstrated an important role for gK in virus replication (8,15,25,32). Only small plaques or foci of infected cells were observed after infection of noncomplementing cells with gK mutants of HSV-1 and PrV (14,25), and productive viral replication was prevented by deletion of VZV gK (32).…”

mentioning

confidence: 99%

“…Based on the model of gK topology (31), different functional domains for gK involved in nucleocapsid envelopment, membrane fusion, virus replication, and egress have been proposed (8). Effects on virus yield, plaque formation, and virus envelopment were tentatively assigned to amino-terminal portions of gK, comprising the N terminus, a cytoplasmic loop, and the second extracellular domain.…”

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confidence: 99%

Pseudorabies Virus Glycoprotein K Requires the UL20 Gene Product for Processing

et al. 2000

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Glycoprotein K (gK) of pseudorabies virus (PrV) has recently been identified as a virion component which is dispensable for viral entry but required for direct cell-to-cell spread. Electron microscopic data suggested a possible function of gK in virus egress by preventing immediate fusion of released virus particles with the plasma membrane (B. G. Klupp, J. Baumeister, P. Dietz, H. Granzow, and T. C. Mettenleiter, J. Virol. 72:1949-1958, 1998). For more detailed analysis, a PrV mutant with a deletion of the UL53 (gK) open reading frame (ORF) from codons 48 to 275 was constructed, and the protein was analyzed with two monoclonal antibodies directed against PrV gK. The salient findings of this report are as follows. (i) From the PrV UL53 ORF, a functional gK is translated only from the first in-frame methionine. From the second in-frame methionine, a nonfunctional product is expressed which is not incorporated into virions. (ii) When constitutively expressed in a stable cell line without other viral proteins, gK is only incompletely processed. After superinfection with gK-deletion mutants, proper processing is restored and mature gK is incorporated into virions. (iii)The UL20 gene product is specifically required for processing of gK. gK is not correctly processed in a UL20 deletion mutant of PrV, and superinfection of gK-expressing cells with PrV-UL20 ؊ does not restore processing. However, all other known structural viral glycoproteins appear to be processed normally in PrV-UL20 ؊ -infected cells. (iv) Coexpression of gK and UL20 restored gK processing at least partially. Thus, our data show that the UL20 gene product is required for proper processing of PrV gK.

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Escape of herpesviruses from the nucleus

Lee

Chen

2010

Reviews in Medical Virology

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The nuclear envelope of eukaryotic cells is composed of double lipid-bilayer membranes, the membrane-connected nuclear pore complexes and an underlying nuclear lamina network. The nuclear pore complexes serve as gates for regulating the transport of macromolecules between cytoplasm and nucleus. The nuclear lamina not only provides an intact meshwork for maintaining the nuclear stiffness but also presents a natural barrier against most DNA viruses. Herpesviruses are large DNA viruses associated with multiple human and animal diseases. The complex herpesviral virion contains more than 30 viral proteins. After viral DNA replication, the newly synthesised genome is packaged into the pre-assembled intranuclear capsid. The nucleocapsid must then transverse through the nuclear envelope to the cytoplasm for the subsequent maturation process. Information regarding how nucleocapsid breaches the rigid nuclear lamina barrier and accesses the inner nuclear membrane for primary envelopment has emerged recently. From the point of view of both viral components and nuclear structure, this review summarises recent advances in the complicated protein-protein interactions and the phosphorylation regulations involved in the nuclear egress of herpesviral nucleocapsids.

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Genetic Analysis of the Role of Herpes Simplex Virus Type 1 Glycoprotein K in Infectious Virus Production and Egress

Cited by 85 publications

References 48 publications

The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection

The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection

Pseudorabies Virus Glycoprotein K Requires the UL20 Gene Product for Processing

Escape of herpesviruses from the nucleus

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