The Herpes Simplex Virus Type 1 UL20 Protein Modulates Membrane Fusion Events during Cytoplasmic Virion Morphogenesis and Virus-Induced Cell Fusion

Foster, Timothy P.; Melancon, Jeffrey M.; Baines, Joel D.; Kousoulas, Konstantin G.

doi:10.1128/jvi.78.10.5347-5357.2004

Cited by 79 publications

(136 citation statements)

References 30 publications

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“…The results of the current study support and extend our previous observations. Deletion of gK has been shown to affect virus yield and plaque size and translocation of the virus from the cytoplasm to the extracellular space (28) and to play a role in virion entry, cytoplasmic virion envelopment, and virus-induced cell fusion (27)(28)(29)(30)(48)(49)(50)(51)(52). These functions of HSV gK are similar to those reported for the gKs of pseudorabies and varicella-zoster virus (53)(54)(55).…”

Section: Discussionsupporting

confidence: 63%

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Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence

Matundan

Mott

Akhtar

et al. 2015

J Virol

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To investigate the role of the signal sequences of herpes simplex virus 1 (HSV-1) gK on virus replication and viral pathogenesis, we constructed recombinant viruses with or without mutations within the signal sequences of gK. These recombinant viruses expressed two additional copies of the mutated (MgK) or native (NgK) form of the gK gene in place of the latency-associated transcript with a myc epitope tag to facilitate detection at their 3= ends. The replication of MgK virus was similar to that of NgK both in vitro and in vivo, as well as in the trigeminal ganglia (TG) of latently infected mice. The levels of gB and gK transcripts in the corneas, TG, and brains of infected mice on days 3 and 5 postinfection were markedly virus and time dependent, as well as tissue specific. Mutation in the signal sequence of gK in MgK virus blocked cell surface expression of gK-myc in rabbit skin cells, increased 50% lethal dose, and decreased corneal scarring in ocularly infected mice compared to the NgK or revertant (RgK) virus. MgK and NgK viruses, and not the RgK virus, showed a reduced extent of explant reactivation at the lower dose of ocular infection but not at the higher dose. However, the time of reactivation was not affected by overexpression of the different forms of gK. Taken together, these results strongly suggest that the 8mer peptide (ITAYGLVL) within the signal sequence of gK promotes cell surface expression of gK in infected cells and ocular pathogenesis in infected mice. IMPORTANCEIn this study, we show for the first time that mutations within the signal sequence of gK blocked cell surface expression of inserted recombinant gK in vitro. Furthermore, this blockage in cell surface expression was correlated with higher 50% lethal dose and less corneal scarring in vivo. Thus, these studies point to a key role for the 8mer within the signal sequence of gK in HSV-1-induced pathogenicity. Herpes simplex virus 1 (HSV-1) infections are among the most frequent serious viral eye infections in the United States and are a major cause of virus-induced blindness (1-3). It is estimated that 70 to 90% of American adults have antibodies to HSV-1 and/or HSV-2 and ca. 25% of these individuals have clinical symptoms upon routine clinical inquiry. HSV-1 is responsible for Ͼ90% of ocular HSV infections (1, 2, 4-7). HSV-1-induced corneal scarring (CS), also broadly referred to as herpes stromal keratitis (HSK), can lead to blindness. Furthermore, HSV-1 is the leading cause of corneal blindness due to an infectious agent in developed countries (1, 2, 4-7). In addition to necrotizing HSK, ocular infection with HSV-1 can cause eye disease ranging in severity from blepharitis, conjunctivitis, and dendritic keratitis to disciform stromal edema (4, 7-11). In the United States, approximately 30,000 people per year suffer recurrent ocular HSV episodes, requiring doctor visits, medication, and in severe cases, corneal transplants.Although it is well established that HSV-1-induced CS is due to immune responses to the virus, the exact...

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Section: Discussionsupporting

confidence: 63%

“…The gK expressed on virions forms a complex with the membrane-associated UL20 viral protein (52,56). HSV-1 mutants that lack gK fail to acquire a cytoplasmic envelope efficiently.…”

Section: Discussionmentioning

confidence: 99%

Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence

Matundan

Mott

Akhtar

et al. 2015

J Virol

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“…UL20 encodes for a transmembrane protein that is required for glycosylation and cell surface expression of gK (70). UL20-null mutants form small plaques in culture (56). Additionally, RNA inhibition of UL20 results in decreased rates of encephalitis following HSV footpad injection in mice (63).…”

Section: Discussionmentioning

confidence: 99%

“…http://dx.doi.org/10.1101/262055 doi: bioRxiv preprint first posted online Feb. 8, 2018; these coding variations that correlate with neonatal CNS disease phenotypes impact viral proteins known to modulate cell-to-cell spread (52)(53)(54)(55)(56) and/or contribute to neurovirulence in mouse models of CNS infection (54,(57)(58)(59)(60)(61)(62)(63) (Figure 7 and Table S2), however, their role in human disease has not been described. Additional variants in proteins not known to be associated with neurovirulence were also found to be associated with neonatal CNS disease.…”

Section: Coding Variations Identified Between Neonatal Hsv-2 Isolatesmentioning

confidence: 99%

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Genotypic and phenotypic diversity within the neonatal HSV-2 population

Akhtar

Bowen

Renner

et al. 2018

Preprint

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Neonates infected with herpes simplex virus (HSV) at the time of birth can have different courses of clinical disease. Approximately half of those infected display manifestations limited to the skin, eyes, or mouth (SEM disease, 45%). However, others develop invasive infections that spread systemically (disseminated, 25%) or to the central nervous system (CNS, 30%); both of which are associated with significant morbidity and mortality. The viral and/or host factors that predispose a neonate to these invasive forms of HSV infection are not known. To define the level of viral diversity within the neonatal population we evaluated ten HSV-2 isolates cultured from neonates with a range of clinical presentations. To assess viral fitness independent of host immune factors, we measured viral growth characteristics of each isolate in cultured cells. We found that HSV-2 isolates displayed diverse in vitro phenotypes. Isolates from neonates with CNS disease were associated with larger average plaque size and enhanced spread through culture, with isolates derived directly from the cerebrospinal fluid (CSF) exhibiting the most robust growth characteristics. We then sequenced the complete viral genomes of all ten neonatal HSV-2 isolates, providing the first insights into HSV genomic diversity in this clinical setting.We found extensive inter-host variation between isolates distributed throughout the HSV-2

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Virus-Induced Cell Fusion and Syncytia Formation

Xie

2023

Results and Problems in Cell Differentiation

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The Herpes Simplex Virus Type 1 UL20 Protein Modulates Membrane Fusion Events during Cytoplasmic Virion Morphogenesis and Virus-Induced Cell Fusion

Abstract: The herpes simplex virus type 1 (HSV-1) UL20 protein is an important determinant for virion morphogenesis and virus-induced cell fusion. A precise deletion of the UL20 gene in the HSV-1 KOS strain was constructed without affecting the adjacent UL20.

Cited by 79 publications

References 30 publications

Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence

Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence

Genotypic and phenotypic diversity within the neonatal HSV-2 population

Virus-Induced Cell Fusion and Syncytia Formation

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