Eintrag weiter verarbeiten
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro
Gespeichert in:
Zeitschriftentitel: | Journal of Virology |
---|---|
Personen und Körperschaften: | , , , , , , |
In: | Journal of Virology, 88, 2014, 16, S. 9391-9405 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society for Microbiology
|
Schlagwörter: |
author_facet |
Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico |
---|---|
author |
Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico |
spellingShingle |
Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico Journal of Virology Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro Virology Insect Science Immunology Microbiology |
author_sort |
noriega, vanessa m. |
spelling |
Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00934-14 <jats:title>ABSTRACT</jats:title><jats:p>The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term<jats:italic>in vitro</jats:italic>model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14<jats:sup>+</jats:sup>monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>HCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14<jats:sup>+</jats:sup>monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This<jats:italic>in vitro</jats:italic>model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.</jats:p> Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental Latency<i>In Vitro</i> Journal of Virology |
doi_str_mv |
10.1128/jvi.00934-14 |
facet_avail |
Online Free |
finc_class_facet |
Medizin Biologie |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTEyOC9qdmkuMDA5MzQtMTQ |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTEyOC9qdmkuMDA5MzQtMTQ |
institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
imprint |
American Society for Microbiology, 2014 |
imprint_str_mv |
American Society for Microbiology, 2014 |
issn |
0022-538X 1098-5514 |
issn_str_mv |
0022-538X 1098-5514 |
language |
English |
mega_collection |
American Society for Microbiology (CrossRef) |
match_str |
noriega2014humancytomegalovirusmodulatesmonocytemediatedinnateimmuneresponsesduringshorttermexperimentallatencyinvitro |
publishDateSort |
2014 |
publisher |
American Society for Microbiology |
recordtype |
ai |
record_format |
ai |
series |
Journal of Virology |
source_id |
49 |
title |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_unstemmed |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_full |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_fullStr |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_full_unstemmed |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_short |
Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_sort |
human cytomegalovirus modulates monocyte-mediated innate immune responses during short-term experimental latency<i>in vitro</i> |
topic |
Virology Insect Science Immunology Microbiology |
url |
http://dx.doi.org/10.1128/jvi.00934-14 |
publishDate |
2014 |
physical |
9391-9405 |
description |
<jats:title>ABSTRACT</jats:title><jats:p>The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term<jats:italic>in vitro</jats:italic>model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14<jats:sup>+</jats:sup>monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>HCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14<jats:sup>+</jats:sup>monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This<jats:italic>in vitro</jats:italic>model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.</jats:p> |
container_issue |
16 |
container_start_page |
9391 |
container_title |
Journal of Virology |
container_volume |
88 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792344284344614912 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T17:05:09.341Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Human+Cytomegalovirus+Modulates+Monocyte-Mediated+Innate+Immune+Responses+during+Short-Term+Experimental+LatencyIn+Vitro&rft.date=2014-08-15&genre=article&issn=1098-5514&volume=88&issue=16&spage=9391&epage=9405&pages=9391-9405&jtitle=Journal+of+Virology&atitle=Human+Cytomegalovirus+Modulates+Monocyte-Mediated+Innate+Immune+Responses+during+Short-Term+Experimental+Latency%3Ci%3EIn+Vitro%3C%2Fi%3E&aulast=Tortorella&aufirst=Domenico&rft_id=info%3Adoi%2F10.1128%2Fjvi.00934-14&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792344284344614912 |
author | Noriega, Vanessa M., Haye, Kester K., Kraus, Thomas A., Kowalsky, Shanna R., Ge, Yongchao, Moran, Thomas M., Tortorella, Domenico |
author_facet | Noriega, Vanessa M., Haye, Kester K., Kraus, Thomas A., Kowalsky, Shanna R., Ge, Yongchao, Moran, Thomas M., Tortorella, Domenico, Noriega, Vanessa M., Haye, Kester K., Kraus, Thomas A., Kowalsky, Shanna R., Ge, Yongchao, Moran, Thomas M., Tortorella, Domenico |
author_sort | noriega, vanessa m. |
container_issue | 16 |
container_start_page | 9391 |
container_title | Journal of Virology |
container_volume | 88 |
description | <jats:title>ABSTRACT</jats:title><jats:p>The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term<jats:italic>in vitro</jats:italic>model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14<jats:sup>+</jats:sup>monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>HCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14<jats:sup>+</jats:sup>monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This<jats:italic>in vitro</jats:italic>model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.</jats:p> |
doi_str_mv | 10.1128/jvi.00934-14 |
facet_avail | Online, Free |
finc_class_facet | Medizin, Biologie |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTEyOC9qdmkuMDA5MzQtMTQ |
imprint | American Society for Microbiology, 2014 |
imprint_str_mv | American Society for Microbiology, 2014 |
institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
issn | 0022-538X, 1098-5514 |
issn_str_mv | 0022-538X, 1098-5514 |
language | English |
last_indexed | 2024-03-01T17:05:09.341Z |
match_str | noriega2014humancytomegalovirusmodulatesmonocytemediatedinnateimmuneresponsesduringshorttermexperimentallatencyinvitro |
mega_collection | American Society for Microbiology (CrossRef) |
physical | 9391-9405 |
publishDate | 2014 |
publishDateSort | 2014 |
publisher | American Society for Microbiology |
record_format | ai |
recordtype | ai |
series | Journal of Virology |
source_id | 49 |
spelling | Noriega, Vanessa M. Haye, Kester K. Kraus, Thomas A. Kowalsky, Shanna R. Ge, Yongchao Moran, Thomas M. Tortorella, Domenico 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00934-14 <jats:title>ABSTRACT</jats:title><jats:p>The ability of human cytomegalovirus (HCMV) to establish lifelong persistence and reactivate from latency is critical to its success as a pathogen. Here we describe a short-term<jats:italic>in vitro</jats:italic>model representing the events surrounding HCMV latency and reactivation in circulating peripheral blood monocytes that was developed in order to study the immunological consequence of latent virus carriage. Infection of human CD14<jats:sup>+</jats:sup>monocytes by HCMV resulted in the immediate establishment of latency, as evidenced by the absence of particular lytic gene expression, the transcription of latency-associated mRNAs, and the maintenance of viral genomes. Latent HCMV induced cellular differentiation to a macrophage lineage, causing production of selective proinflammatory cytokines and myeloid-cell chemoattractants that most likely play a role in virus dissemination in the host. Analysis of global cellular gene expression revealed activation of innate immune responses and the modulation of protein and lipid synthesis to accommodate latent HCMV infection. Remarkably, monocytes harboring latent virus exhibited selective responses to secondary stimuli known to induce an antiviral state. Furthermore, when challenged with type I and II interferon, latently infected cells demonstrated a blockade of signaling at the level of STAT1 phosphorylation. The data demonstrate that HCMV reprograms specific cellular pathways in monocytes, most notably innate immune responses, which may play a role in the establishment of, maintenance of, and reactivation from latency. The modulation of innate immune responses is likely a viral evasion strategy contributing to viral dissemination and pathogenesis in the host.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>HCMV has the ability to establish a lifelong infection within the host, a phenomenon termed latency. We have established a short-term model system in human peripheral blood monocytes to study the immunological relevance of latent virus carriage. Infection of CD14<jats:sup>+</jats:sup>monocytes by HCMV results in the generation of latency-specific transcripts, maintenance of viral genomes, and the capacity to reenter the lytic cycle. During short-term latency in monocytes the virus initiates a program of differentiation to inflammatory macrophages that coincides with the modulation of cytokine secretion and specific cellular processes. HCMV-infected monocytes are hindered in their capacity to exert normal immunoprotective mechanisms. Additionally, latent virus disrupts type I and II interferon signaling at the level of STAT1 phosphorylation. This<jats:italic>in vitro</jats:italic>model system can significantly contribute to our understanding of the molecular and inflammatory factors that initiate HCMV reactivation in the host and allow the development of strategies to eradicate virus persistence.</jats:p> Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental Latency<i>In Vitro</i> Journal of Virology |
spellingShingle | Noriega, Vanessa M., Haye, Kester K., Kraus, Thomas A., Kowalsky, Shanna R., Ge, Yongchao, Moran, Thomas M., Tortorella, Domenico, Journal of Virology, Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro, Virology, Insect Science, Immunology, Microbiology |
title | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_full | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_fullStr | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_full_unstemmed | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_short | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
title_sort | human cytomegalovirus modulates monocyte-mediated innate immune responses during short-term experimental latency<i>in vitro</i> |
title_unstemmed | Human Cytomegalovirus Modulates Monocyte-Mediated Innate Immune Responses during Short-Term Experimental LatencyIn Vitro |
topic | Virology, Insect Science, Immunology, Microbiology |
url | http://dx.doi.org/10.1128/jvi.00934-14 |