Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation

Jillian C. Carmichael, Jason Starkey, Dan Zhang, Akua Sarfo, Pooja Chadha, John Wills, Jun Han

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) plays a key role in multiple events during infection including virus entry, cell-to-cell spread, and virus-induced syncytia formation. Here, we provide evidence that an arginine/lysine cluster located at the transmembrane-cytoplasm interface of gD critically contributes to viral spread and cell-cell fusion. Our studies began with the discovery that packaging of gD into virions is almost completely blocked in the absence of tegument protein UL16. We subsequently identified a novel, direct, and regulated interaction between UL16 and gD, but this was not important for syncytia formation. However, a mutational analysis of the membrane-proximal basic residues of gD revealed that they are needed for the gBsyn phenotype, salubrinal-induced fusion of HSV-infected cells, and cell-to-cell spread. Finally, we found that these same gD tail basic residues are not required for cell fusion induced by a gKsyn variant.

Original languageEnglish (US)
Pages (from-to)64-76
Number of pages13
JournalVirology
Volume527
DOIs
StatePublished - Jan 15 2019

Fingerprint

Human Herpesvirus 1
Product Packaging
Giant Cells
Glycoproteins
Proteins
Cell Fusion
Virus Internalization
Virion
Lysine
Arginine
Human herpesvirus 1 glycoprotein D
Cytoplasm
Viruses
Phenotype
Membranes
Infection

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Carmichael, Jillian C. ; Starkey, Jason ; Zhang, Dan ; Sarfo, Akua ; Chadha, Pooja ; Wills, John ; Han, Jun. / Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation. In: Virology. 2019 ; Vol. 527. pp. 64-76.
@article{a0a9a34308fd432287ea5291317e1fad,
title = "Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation",
abstract = "Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) plays a key role in multiple events during infection including virus entry, cell-to-cell spread, and virus-induced syncytia formation. Here, we provide evidence that an arginine/lysine cluster located at the transmembrane-cytoplasm interface of gD critically contributes to viral spread and cell-cell fusion. Our studies began with the discovery that packaging of gD into virions is almost completely blocked in the absence of tegument protein UL16. We subsequently identified a novel, direct, and regulated interaction between UL16 and gD, but this was not important for syncytia formation. However, a mutational analysis of the membrane-proximal basic residues of gD revealed that they are needed for the gBsyn phenotype, salubrinal-induced fusion of HSV-infected cells, and cell-to-cell spread. Finally, we found that these same gD tail basic residues are not required for cell fusion induced by a gKsyn variant.",
author = "Carmichael, {Jillian C.} and Jason Starkey and Dan Zhang and Akua Sarfo and Pooja Chadha and John Wills and Jun Han",
year = "2019",
month = "1",
day = "15",
doi = "10.1016/j.virol.2018.09.018",
language = "English (US)",
volume = "527",
pages = "64--76",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",

}

Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation. / Carmichael, Jillian C.; Starkey, Jason; Zhang, Dan; Sarfo, Akua; Chadha, Pooja; Wills, John; Han, Jun.

In: Virology, Vol. 527, 15.01.2019, p. 64-76.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation

AU - Carmichael, Jillian C.

AU - Starkey, Jason

AU - Zhang, Dan

AU - Sarfo, Akua

AU - Chadha, Pooja

AU - Wills, John

AU - Han, Jun

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) plays a key role in multiple events during infection including virus entry, cell-to-cell spread, and virus-induced syncytia formation. Here, we provide evidence that an arginine/lysine cluster located at the transmembrane-cytoplasm interface of gD critically contributes to viral spread and cell-cell fusion. Our studies began with the discovery that packaging of gD into virions is almost completely blocked in the absence of tegument protein UL16. We subsequently identified a novel, direct, and regulated interaction between UL16 and gD, but this was not important for syncytia formation. However, a mutational analysis of the membrane-proximal basic residues of gD revealed that they are needed for the gBsyn phenotype, salubrinal-induced fusion of HSV-infected cells, and cell-to-cell spread. Finally, we found that these same gD tail basic residues are not required for cell fusion induced by a gKsyn variant.

AB - Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) plays a key role in multiple events during infection including virus entry, cell-to-cell spread, and virus-induced syncytia formation. Here, we provide evidence that an arginine/lysine cluster located at the transmembrane-cytoplasm interface of gD critically contributes to viral spread and cell-cell fusion. Our studies began with the discovery that packaging of gD into virions is almost completely blocked in the absence of tegument protein UL16. We subsequently identified a novel, direct, and regulated interaction between UL16 and gD, but this was not important for syncytia formation. However, a mutational analysis of the membrane-proximal basic residues of gD revealed that they are needed for the gBsyn phenotype, salubrinal-induced fusion of HSV-infected cells, and cell-to-cell spread. Finally, we found that these same gD tail basic residues are not required for cell fusion induced by a gKsyn variant.

UR - http://www.scopus.com/inward/record.url?scp=85056743149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056743149&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2018.09.018

DO - 10.1016/j.virol.2018.09.018

M3 - Article

C2 - 30465930

AN - SCOPUS:85056743149

VL - 527

SP - 64

EP - 76

JO - Virology

JF - Virology

SN - 0042-6822

ER -