The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype

Akua Sarfo, Jason Starkey, Erica Mellinger, Dan Zhang, Pooja Chadha, Jillian Carmichael, John W. Wills

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20Syn and UL24Syn. To test whether UL21 is needed only for the A855V mutant, additional gBSyn derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gBSyn phenotype. This is the first example of a differential requirement for a viral protein across the four syn loci.

Original languageEnglish (US)
Article numbere01161-17
JournalJournal of virology
Volume91
Issue number21
DOIs
StatePublished - Nov 1 2017

Fingerprint

Human herpesvirus 1
Glycoproteins
Human Herpesvirus 2
Human Herpesvirus 1
Phenotype
phenotype
glycoproteins
mutants
Viruses
Mutation
proteins
Capsid
Viral Proteins
Virus Replication
Infection
mutation
viruses
loci
capsid
viral proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Sarfo, Akua ; Starkey, Jason ; Mellinger, Erica ; Zhang, Dan ; Chadha, Pooja ; Carmichael, Jillian ; Wills, John W. / The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype. In: Journal of virology. 2017 ; Vol. 91, No. 21.
@article{1f9fbcaa275f4e09b9449189eee6812f,
title = "The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype",
abstract = "The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20Syn and UL24Syn. To test whether UL21 is needed only for the A855V mutant, additional gBSyn derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gBSyn phenotype. This is the first example of a differential requirement for a viral protein across the four syn loci.",
author = "Akua Sarfo and Jason Starkey and Erica Mellinger and Dan Zhang and Pooja Chadha and Jillian Carmichael and Wills, {John W.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1128/JVI.01161-17",
language = "English (US)",
volume = "91",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "21",

}

The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype. / Sarfo, Akua; Starkey, Jason; Mellinger, Erica; Zhang, Dan; Chadha, Pooja; Carmichael, Jillian; Wills, John W.

In: Journal of virology, Vol. 91, No. 21, e01161-17, 01.11.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype

AU - Sarfo, Akua

AU - Starkey, Jason

AU - Mellinger, Erica

AU - Zhang, Dan

AU - Chadha, Pooja

AU - Carmichael, Jillian

AU - Wills, John W.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20Syn and UL24Syn. To test whether UL21 is needed only for the A855V mutant, additional gBSyn derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gBSyn phenotype. This is the first example of a differential requirement for a viral protein across the four syn loci.

AB - The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20Syn and UL24Syn. To test whether UL21 is needed only for the A855V mutant, additional gBSyn derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gBSyn phenotype. This is the first example of a differential requirement for a viral protein across the four syn loci.

UR - http://www.scopus.com/inward/record.url?scp=85031097844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031097844&partnerID=8YFLogxK

U2 - 10.1128/JVI.01161-17

DO - 10.1128/JVI.01161-17

M3 - Article

C2 - 28794039

AN - SCOPUS:85031097844

VL - 91

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 21

M1 - e01161-17

ER -