Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present dur...

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Autores principales:	Yike Jiang, Chaya D. Patel, Richard Manivanh, Brian North, Iara M. Backes, David A. Posner, Francesca Gilli, Andrew R. Pachner, Lananh N. Nguyen, David A. Leib
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	herpes simplex virus maternal antibody neonatal infection neuroimmunology trigeminal ganglion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6dbbb3e5cd3f47c88be594817ba86771
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spelling	oai:doaj.org-article:6dbbb3e5cd3f47c88be594817ba867712021-11-15T15:51:44ZMaternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease10.1128/mBio.00678-172150-7511https://doaj.org/article/6dbbb3e5cd3f47c88be594817ba867712017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00678-17https://doaj.org/toc/2150-7511ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.Yike JiangChaya D. PatelRichard ManivanhBrian NorthIara M. BackesDavid A. PosnerFrancesca GilliAndrew R. PachnerLananh N. NguyenDavid A. LeibAmerican Society for Microbiologyarticleherpes simplex virusmaternal antibodyneonatal infectionneuroimmunologytrigeminal ganglionMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	herpes simplex virus maternal antibody neonatal infection neuroimmunology trigeminal ganglion Microbiology QR1-502
spellingShingle	herpes simplex virus maternal antibody neonatal infection neuroimmunology trigeminal ganglion Microbiology QR1-502 Yike Jiang Chaya D. Patel Richard Manivanh Brian North Iara M. Backes David A. Posner Francesca Gilli Andrew R. Pachner Lananh N. Nguyen David A. Leib Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
description	ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.
format	article
author	Yike Jiang Chaya D. Patel Richard Manivanh Brian North Iara M. Backes David A. Posner Francesca Gilli Andrew R. Pachner Lananh N. Nguyen David A. Leib
author_facet	Yike Jiang Chaya D. Patel Richard Manivanh Brian North Iara M. Backes David A. Posner Francesca Gilli Andrew R. Pachner Lananh N. Nguyen David A. Leib
author_sort	Yike Jiang
title	Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
title_short	Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
title_full	Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
title_fullStr	Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
title_full_unstemmed	Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease
title_sort	maternal antiviral immunoglobulin accumulates in neural tissue of neonates to prevent hsv neurological disease
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/6dbbb3e5cd3f47c88be594817ba86771
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Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

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