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 journalArticlepeer-review

26 Scopus citations


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
Article numbere01161-17
JournalJournal of Virology
Issue number21
StatePublished - 1 Nov 2017
Externally publishedYes


  • Glycoproteins
  • HSV-1
  • Syncytia


Dive into the research topics of 'The UL21 tegument protein of herpes simplex virus 1 is differentially required for the syncytial phenotype'. Together they form a unique fingerprint.

Cite this