Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics
Abstract Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12597-4 |
| _version_ | 1811341375759712256 |
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| author | Antoine Rousseau Oscar Haigh Roger Legrand Jean-Louis Palgen Julien Lemaitre Claire Deback Noémie Oziol Patrick Lomonte Marc Labetoulle |
| author_facet | Antoine Rousseau Oscar Haigh Roger Legrand Jean-Louis Palgen Julien Lemaitre Claire Deback Noémie Oziol Patrick Lomonte Marc Labetoulle |
| author_sort | Antoine Rousseau |
| collection | DOAJ |
| description | Abstract Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences. We previously engendered an acute disease-free, non-reactivating latent state in mice when challenged with virulent HSV-1 in orofacial mucosa, by priming with non-neurovirulent HSV-1 (TKdel) before the challenge. Herein, we define the local immune infiltration and inflammatory chemokine production changes after virulent HSV-1 challenge, which were elicited by TKdel prime. Heightened immunosurveillance before virulent challenge, and early enhanced lymphocyte-enriched infiltration of the challenged lip were induced, which corresponded to attenuation of inflammation in the TG and enhanced viral control. Furthermore, classical latent-phase T cell persistence around latent HSV-1 reservoirs were severely reduced. These findings identify the immune processes that are likely to be responsible for establishing non-reactivating latent HSV-1 reservoirs. Stopping reactivation is essential for development of efficient vaccine strategies against HSV-1. |
| first_indexed | 2024-04-13T18:54:37Z |
| format | Article |
| id | doaj.art-759feb6d36e04fe28cf79e556fcd4273 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T18:54:37Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-759feb6d36e04fe28cf79e556fcd42732022-12-22T02:34:18ZengNature PortfolioScientific Reports2045-23222022-05-0112111410.1038/s41598-022-12597-4Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamicsAntoine Rousseau0Oscar Haigh1Roger Legrand2Jean-Louis Palgen3Julien Lemaitre4Claire Deback5Noémie Oziol6Patrick Lomonte7Marc Labetoulle8Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Service de Virologie, Hôpital Paul Brousse, Université Paris-Saclay, APHPCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Institut NeuroMyoGène-Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U 1513, Université Claude Bernard Lyon 1, Team Chromatin Dynamics, Nuclear Domains, VirusCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB), Commissariat à l’énergie Atomique et Aux Énergies Renouvelables, Université Paris-Saclay, INSERM U1184Abstract Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences. We previously engendered an acute disease-free, non-reactivating latent state in mice when challenged with virulent HSV-1 in orofacial mucosa, by priming with non-neurovirulent HSV-1 (TKdel) before the challenge. Herein, we define the local immune infiltration and inflammatory chemokine production changes after virulent HSV-1 challenge, which were elicited by TKdel prime. Heightened immunosurveillance before virulent challenge, and early enhanced lymphocyte-enriched infiltration of the challenged lip were induced, which corresponded to attenuation of inflammation in the TG and enhanced viral control. Furthermore, classical latent-phase T cell persistence around latent HSV-1 reservoirs were severely reduced. These findings identify the immune processes that are likely to be responsible for establishing non-reactivating latent HSV-1 reservoirs. Stopping reactivation is essential for development of efficient vaccine strategies against HSV-1.https://doi.org/10.1038/s41598-022-12597-4 |
| spellingShingle | Antoine Rousseau Oscar Haigh Roger Legrand Jean-Louis Palgen Julien Lemaitre Claire Deback Noémie Oziol Patrick Lomonte Marc Labetoulle Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics Scientific Reports |
| title | Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics |
| title_full | Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics |
| title_fullStr | Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics |
| title_full_unstemmed | Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics |
| title_short | Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics |
| title_sort | initial tk deficient hsv 1 infection in the lip alters contralateral lip challenge immune dynamics |
| url | https://doi.org/10.1038/s41598-022-12597-4 |
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