Domain interaction studies of herpes simplex virus 1 tegument protein UL16 reveal its interaction with mitochondria

Pooja Chadha, Akua Sarfo, Dan Zhang, Thomas Abraham, Jillian Carmichael, Jun Han, John W. Wills

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined.

Original languageEnglish (US)
Article numbere01995-16
JournalJournal of virology
Volume91
Issue number2
DOIs
StatePublished - Jan 1 2017

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Human herpesvirus 1
Human Herpesvirus 1
Mitochondria
mitochondria
Proteins
proteins
cells
Herpesviridae
viral proteins
Viral Proteins
transfection
Organelles
Transfection
organelles
glycoproteins
electron microscopy
Electron Microscopy
Glycoproteins
image analysis
assays

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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title = "Domain interaction studies of herpes simplex virus 1 tegument protein UL16 reveal its interaction with mitochondria",
abstract = "The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined.",
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Domain interaction studies of herpes simplex virus 1 tegument protein UL16 reveal its interaction with mitochondria. / Chadha, Pooja; Sarfo, Akua; Zhang, Dan; Abraham, Thomas; Carmichael, Jillian; Han, Jun; Wills, John W.

In: Journal of virology, Vol. 91, No. 2, e01995-16, 01.01.2017.

Research output: Contribution to journalArticle

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AU - Han, Jun

AU - Wills, John W.

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