Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread

Liang Tzung Lin, Ting Ying Chen, Chueh Yao Chung, Ryan S. Noyce, T. Bruce Grindley, Craig McCormick, Ta Chen Lin, Guey Horng Wang, Chun Ching Lin, Christopher D. Richardson

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.

Original languageEnglish
Pages (from-to)4386-4398
Number of pages13
JournalJournal of Virology
Volume85
Issue number9
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

Hydrolyzable Tannins
Human herpesvirus 1
Virus Internalization
glycosaminoglycans
Human Herpesvirus 1
Glycosaminoglycans
tannins
glycoproteins
Glycoproteins
acids
Tannins
cells
Heparitin Sulfate
Antiviral Agents
Combretaceae
Viral Drug Resistance
Terminalia chebula
Terminalia
immunocompromised population
chondroitin sulfate

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread. / Lin, Liang Tzung; Chen, Ting Ying; Chung, Chueh Yao; Noyce, Ryan S.; Grindley, T. Bruce; McCormick, Craig; Lin, Ta Chen; Wang, Guey Horng; Lin, Chun Ching; Richardson, Christopher D.

In: Journal of Virology, Vol. 85, No. 9, 05.2011, p. 4386-4398.

Research output: Contribution to journalArticle

Lin, Liang Tzung ; Chen, Ting Ying ; Chung, Chueh Yao ; Noyce, Ryan S. ; Grindley, T. Bruce ; McCormick, Craig ; Lin, Ta Chen ; Wang, Guey Horng ; Lin, Chun Ching ; Richardson, Christopher D. / Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread. In: Journal of Virology. 2011 ; Vol. 85, No. 9. pp. 4386-4398.
@article{f2495574f26d42848a3b50d6fbab3e54,
title = "Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread",
abstract = "Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.",
author = "Lin, {Liang Tzung} and Chen, {Ting Ying} and Chung, {Chueh Yao} and Noyce, {Ryan S.} and Grindley, {T. Bruce} and Craig McCormick and Lin, {Ta Chen} and Wang, {Guey Horng} and Lin, {Chun Ching} and Richardson, {Christopher D.}",
year = "2011",
month = "5",
doi = "10.1128/JVI.01492-10",
language = "English",
volume = "85",
pages = "4386--4398",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread

AU - Lin, Liang Tzung

AU - Chen, Ting Ying

AU - Chung, Chueh Yao

AU - Noyce, Ryan S.

AU - Grindley, T. Bruce

AU - McCormick, Craig

AU - Lin, Ta Chen

AU - Wang, Guey Horng

AU - Lin, Chun Ching

AU - Richardson, Christopher D.

PY - 2011/5

Y1 - 2011/5

N2 - Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.

AB - Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.

UR - http://www.scopus.com/inward/record.url?scp=79955409003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955409003&partnerID=8YFLogxK

U2 - 10.1128/JVI.01492-10

DO - 10.1128/JVI.01492-10

M3 - Article

C2 - 21307190

AN - SCOPUS:79955409003

VL - 85

SP - 4386

EP - 4398

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

ER -