The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection

Shaohui Wang, Kevin R. Mott, Marianne Cilluffo, Casey L. Kilpatrick, Shoko Murakami, Alexander V. Ljubimov, Konstantin G. Kousoulas, Sita Awasthi, Bernhard Luscher, Homayon Ghiasi

Research output: Contribution to journalArticle

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Abstract

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 (ZDHHC3) 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.

Original languageEnglish (US)
Article numbere01599-17
JournalJournal of virology
Volume92
Issue number4
DOIs
StatePublished - Feb 1 2018

Fingerprint

Human herpesvirus 1
Human Herpesvirus 1
Virus Diseases
mice
infection
Lipoylation
Zinc Fingers
Virus Replication
zinc finger motif
Virion
virion
Glycoproteins
fibroblasts
Fibroblasts
glycoproteins
Virus Latency
Virus Release
Trigeminal Ganglion
viruses
Capsid Proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Wang, S., Mott, K. R., Cilluffo, M., Kilpatrick, C. L., Murakami, S., Ljubimov, A. V., ... Ghiasi, H. (2018). The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection. Journal of virology, 92(4), [e01599-17]. https://doi.org/10.1128/JVI.01599-17
Wang, Shaohui ; Mott, Kevin R. ; Cilluffo, Marianne ; Kilpatrick, Casey L. ; Murakami, Shoko ; Ljubimov, Alexander V. ; Kousoulas, Konstantin G. ; Awasthi, Sita ; Luscher, Bernhard ; Ghiasi, Homayon. / The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection. In: Journal of virology. 2018 ; Vol. 92, No. 4.
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abstract = "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 (ZDHHC3) 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.",
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Wang, S, Mott, KR, Cilluffo, M, Kilpatrick, CL, Murakami, S, Ljubimov, AV, Kousoulas, KG, Awasthi, S, Luscher, B & Ghiasi, H 2018, 'The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection', Journal of virology, vol. 92, no. 4, e01599-17. https://doi.org/10.1128/JVI.01599-17

The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection. / Wang, Shaohui; Mott, Kevin R.; Cilluffo, Marianne; Kilpatrick, Casey L.; Murakami, Shoko; Ljubimov, Alexander V.; Kousoulas, Konstantin G.; Awasthi, Sita; Luscher, Bernhard; Ghiasi, Homayon.

In: Journal of virology, Vol. 92, No. 4, e01599-17, 01.02.2018.

Research output: Contribution to journalArticle

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T1 - The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection

AU - Wang, Shaohui

AU - Mott, Kevin R.

AU - Cilluffo, Marianne

AU - Kilpatrick, Casey L.

AU - Murakami, Shoko

AU - Ljubimov, Alexander V.

AU - Kousoulas, Konstantin G.

AU - Awasthi, Sita

AU - Luscher, Bernhard

AU - Ghiasi, Homayon

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N2 - 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 (ZDHHC3) 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.

AB - 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 (ZDHHC3) 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.

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