Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs.
METHODOLOGY/PRINCIPAL FINDINGS:The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed ra...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0004023 https://doaj.org/article/d57e5110474d4cc09507b32dd391ed1c |
id |
ftdoajarticles:oai:doaj.org/article:d57e5110474d4cc09507b32dd391ed1c |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:d57e5110474d4cc09507b32dd391ed1c 2023-05-15T15:16:19+02:00 Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. Clement W Gnanadurai Yang Yang Ying Huang Zhenguang Li Christina M Leyson Tanya L Cooper Simon R Platt Stephen B Harvey Douglas C Hooper Milosz Faber Zhen F Fu 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004023 https://doaj.org/article/d57e5110474d4cc09507b32dd391ed1c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4546273?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004023 https://doaj.org/article/d57e5110474d4cc09507b32dd391ed1c PLoS Neglected Tropical Diseases, Vol 9, Iss 8, p e0004023 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004023 2022-12-31T00:02:36Z METHODOLOGY/PRINCIPAL FINDINGS:The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT) immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM) immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB) permeability, which is relevant to the passage of immune effectors from periphery into the CNS. CONCLUSIONS/SIGNIFICANCE:IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies. Thus the failure to activate protective immunity is one of the important features of RABV pathogenesis in dogs. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 8 e0004023 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Clement W Gnanadurai Yang Yang Ying Huang Zhenguang Li Christina M Leyson Tanya L Cooper Simon R Platt Stephen B Harvey Douglas C Hooper Milosz Faber Zhen F Fu Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
METHODOLOGY/PRINCIPAL FINDINGS:The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT) immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM) immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB) permeability, which is relevant to the passage of immune effectors from periphery into the CNS. CONCLUSIONS/SIGNIFICANCE:IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies. Thus the failure to activate protective immunity is one of the important features of RABV pathogenesis in dogs. |
format |
Article in Journal/Newspaper |
author |
Clement W Gnanadurai Yang Yang Ying Huang Zhenguang Li Christina M Leyson Tanya L Cooper Simon R Platt Stephen B Harvey Douglas C Hooper Milosz Faber Zhen F Fu |
author_facet |
Clement W Gnanadurai Yang Yang Ying Huang Zhenguang Li Christina M Leyson Tanya L Cooper Simon R Platt Stephen B Harvey Douglas C Hooper Milosz Faber Zhen F Fu |
author_sort |
Clement W Gnanadurai |
title |
Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
title_short |
Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
title_full |
Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
title_fullStr |
Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
title_full_unstemmed |
Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs. |
title_sort |
differential host immune responses after infection with wild-type or lab-attenuated rabies viruses in dogs. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004023 https://doaj.org/article/d57e5110474d4cc09507b32dd391ed1c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 8, p e0004023 (2015) |
op_relation |
http://europepmc.org/articles/PMC4546273?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004023 https://doaj.org/article/d57e5110474d4cc09507b32dd391ed1c |
op_doi |
https://doi.org/10.1371/journal.pntd.0004023 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
8 |
container_start_page |
e0004023 |
_version_ |
1766346616188436480 |