Opposing effects of bacitracin on human papillomavirus type 16 infection: Enhancement of binding and entry and inhibition of endosomal penetration

Samuel K Campos, Janice A. Chapman, Martin J. Deymier, Matthew P. Bronnimann, Michelle A. Ozbune

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Cell invasion by human papillomavirus type 16 (HPV16) is a complex process relying on multiple host cell factors. Here we describe an investigation into the role of cellular protein disulfide isomerases (PDIs) by studying the effects of the commonly used PDI inhibitor bacitracin on HPV16 infection. Bacitracin caused an unusual time-dependent opposing effect on viral infection. Enhanced cellular binding and entry were observed at early times of infection, while inhibition was observed at later times postentry. Bacitracin was rapidly taken up by host cells and colocalized with HPV16 at late times of infection. Bacitracin had no deleterious effect on HPV16 entry, capsid disassembly, exposure of L1/L2 epitopes, or lysosomal trafficking but caused a stark inhibition of L2/viral DNA (vDNA) endosomal penetration and accumulation at nuclear PML bodies. γ-Secretase has recently been implicated in the endosomal penetration of L2/vDNA, but bacitracin had no effect on γ-secretase activity, indicating that blockage of this step occurs through a γ-secretase-independent mechanism. Transient treatment with the reductantβ-mercaptoethanol (β-ME) was able to partially rescue the virus from bacitracin, suggesting the involvement of a cellular reductase activity in HPV16 infection. Small interfering RNA (siRNA) knockdown of cellular PDI and the related PDI family members ERp57 and ERp72 reveals a potential role for PDI and ERp72 in HPV infection.

Original languageEnglish (US)
Pages (from-to)4169-4181
Number of pages13
JournalJournal of Virology
Volume86
Issue number8
DOIs
StatePublished - Apr 2012

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Bacitracin
bacitracin
Papillomavirus Infections
Human papillomavirus 16
protein disulfide-isomerase
Papillomaviridae
Protein Disulfide-Isomerases
Amyloid Precursor Protein Secretases
infection
Viral DNA
Infection
cell invasion
reducing agents
capsid
Mercaptoethanol
Capsid
Reducing Agents
DNA
Virus Diseases
small interfering RNA

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Opposing effects of bacitracin on human papillomavirus type 16 infection : Enhancement of binding and entry and inhibition of endosomal penetration. / Campos, Samuel K; Chapman, Janice A.; Deymier, Martin J.; Bronnimann, Matthew P.; Ozbune, Michelle A.

In: Journal of Virology, Vol. 86, No. 8, 04.2012, p. 4169-4181.

Research output: Contribution to journalArticle

Campos, Samuel K ; Chapman, Janice A. ; Deymier, Martin J. ; Bronnimann, Matthew P. ; Ozbune, Michelle A. / Opposing effects of bacitracin on human papillomavirus type 16 infection : Enhancement of binding and entry and inhibition of endosomal penetration. In: Journal of Virology. 2012 ; Vol. 86, No. 8. pp. 4169-4181.
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