A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies
ABSTRACT We have shown that the herpes simplex virus 1 (HSV-1) gK gene is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglion neuroinvasion in mice (A. T. David, A. Baghian, T. P. Foster, V. N. Chouljenko, and K. G. Kousoulas, Curr. Eye Res. 33:455–467, 2...
Guardado en:
Autores principales: | , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
American Society for Microbiology
2012
|
Materias: | |
Acceso en línea: | https://doaj.org/article/00ccbafdfdde420d85e13f8c24fc401d |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:00ccbafdfdde420d85e13f8c24fc401d |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:00ccbafdfdde420d85e13f8c24fc401d2021-11-15T15:39:09ZA Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies10.1128/mBio.00144-122150-7511https://doaj.org/article/00ccbafdfdde420d85e13f8c24fc401d2012-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00144-12https://doaj.org/toc/2150-7511ABSTRACT We have shown that the herpes simplex virus 1 (HSV-1) gK gene is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglion neuroinvasion in mice (A. T. David, A. Baghian, T. P. Foster, V. N. Chouljenko, and K. G. Kousoulas, Curr. Eye Res. 33:455–467, 2008). To further investigate the role of gK in neuronal infection, we utilized a microfluidic chamber system separating neuronal cell bodies and axonal termini. HSV-1 (McKrae) engineered virus constitutively expressing enhanced green fluorescence protein (GFP) was efficiently transmitted in both a retrograde and an anterograde manner. These results were corroborated by expression of virion structural proteins in either chamber, as well as detection of viral genomes and infectious viruses. In contrast, efficient infection of either chamber with a gK-null virus did not result in infection of the apposed chamber. These results show that gK is an important determinant in virion axonal infection. Moreover, the inability of the gK-null virus to be transmitted in an anterograde manner suggests that virions acquire cytoplasmic envelopes prior to entering axons. IMPORTANCE Herpes simplex virus 1 (HSV-1) enters mucosal epithelial cells and neurons via fusion of the viral envelope with cellular membranes, mediated by viral glycoprotein B (gB) in cooperation with other viral glycoproteins. Retrograde transport of virions to neuronal cell bodies (somata) establishes lifelong latent infection in ganglionic neurons. We have previously reported that gK binds gB and is required for gB-mediated membrane fusion (Jambunatathan et al., J. Virol. 85:12910–12918, 2011; V. N. Chouljenko, A. V. Iyer, S. Chowdhury, J. Kim, and K. G. Kousoulas, J. Virol. 84:8596–8606, 2010). In the current study, we constructed a recombinant virus with the gK gene deleted in the highly virulent ocular HSV-1 strain McKrae. This recombinant virus failed to infect rat ganglionic neuronal axons alone or cocultured with Vero cells in microfluidic chambers. In addition, lack of gK expression prevented anterograde transmission of virions. These results suggest that gK is a critical determinant for neuronal infection and transmission.Andrew T. DavidAhmad SaiedAnu CharlesRamesh SubramanianVladimir N. ChouljenkoKonstantin G. KousoulasAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 4 (2012) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Microbiology QR1-502 |
spellingShingle |
Microbiology QR1-502 Andrew T. David Ahmad Saied Anu Charles Ramesh Subramanian Vladimir N. Chouljenko Konstantin G. Kousoulas A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
description |
ABSTRACT We have shown that the herpes simplex virus 1 (HSV-1) gK gene is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglion neuroinvasion in mice (A. T. David, A. Baghian, T. P. Foster, V. N. Chouljenko, and K. G. Kousoulas, Curr. Eye Res. 33:455–467, 2008). To further investigate the role of gK in neuronal infection, we utilized a microfluidic chamber system separating neuronal cell bodies and axonal termini. HSV-1 (McKrae) engineered virus constitutively expressing enhanced green fluorescence protein (GFP) was efficiently transmitted in both a retrograde and an anterograde manner. These results were corroborated by expression of virion structural proteins in either chamber, as well as detection of viral genomes and infectious viruses. In contrast, efficient infection of either chamber with a gK-null virus did not result in infection of the apposed chamber. These results show that gK is an important determinant in virion axonal infection. Moreover, the inability of the gK-null virus to be transmitted in an anterograde manner suggests that virions acquire cytoplasmic envelopes prior to entering axons. IMPORTANCE Herpes simplex virus 1 (HSV-1) enters mucosal epithelial cells and neurons via fusion of the viral envelope with cellular membranes, mediated by viral glycoprotein B (gB) in cooperation with other viral glycoproteins. Retrograde transport of virions to neuronal cell bodies (somata) establishes lifelong latent infection in ganglionic neurons. We have previously reported that gK binds gB and is required for gB-mediated membrane fusion (Jambunatathan et al., J. Virol. 85:12910–12918, 2011; V. N. Chouljenko, A. V. Iyer, S. Chowdhury, J. Kim, and K. G. Kousoulas, J. Virol. 84:8596–8606, 2010). In the current study, we constructed a recombinant virus with the gK gene deleted in the highly virulent ocular HSV-1 strain McKrae. This recombinant virus failed to infect rat ganglionic neuronal axons alone or cocultured with Vero cells in microfluidic chambers. In addition, lack of gK expression prevented anterograde transmission of virions. These results suggest that gK is a critical determinant for neuronal infection and transmission. |
format |
article |
author |
Andrew T. David Ahmad Saied Anu Charles Ramesh Subramanian Vladimir N. Chouljenko Konstantin G. Kousoulas |
author_facet |
Andrew T. David Ahmad Saied Anu Charles Ramesh Subramanian Vladimir N. Chouljenko Konstantin G. Kousoulas |
author_sort |
Andrew T. David |
title |
A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
title_short |
A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
title_full |
A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
title_fullStr |
A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
title_full_unstemmed |
A Herpes Simplex Virus 1 (McKrae) Mutant Lacking the Glycoprotein K Gene Is Unable To Infect via Neuronal Axons and Egress from Neuronal Cell Bodies |
title_sort |
herpes simplex virus 1 (mckrae) mutant lacking the glycoprotein k gene is unable to infect via neuronal axons and egress from neuronal cell bodies |
publisher |
American Society for Microbiology |
publishDate |
2012 |
url |
https://doaj.org/article/00ccbafdfdde420d85e13f8c24fc401d |
work_keys_str_mv |
AT andrewtdavid aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT ahmadsaied aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT anucharles aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT rameshsubramanian aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT vladimirnchouljenko aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT konstantingkousoulas aherpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT andrewtdavid herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT ahmadsaied herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT anucharles herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT rameshsubramanian herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT vladimirnchouljenko herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies AT konstantingkousoulas herpessimplexvirus1mckraemutantlackingtheglycoproteinkgeneisunabletoinfectvianeuronalaxonsandegressfromneuronalcellbodies |
_version_ |
1718427744719601664 |