Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus

Abstract Background Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV causes a bi-phasic illness in mice where primary replication in lymphoid organs is followed by entry into the central nervous system (CNS). The CNS phase of infection is marked by encepha...

Full description

Bibliographic Details
Main Authors: Paridhi Gupta, Anuj Sharma, Jing Han, Amy Yang, Manish Bhomia, Barbara Knollmann-Ritschel, Raj K Puri, Radha K Maheshwari
Format: Article
Language:English
Published: BMC 2017-04-01
Series:BMC Infectious Diseases
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12879-017-2355-3
id doaj-9ca25e478e9b4432b4fb48e7fe4f4b7a
record_format Article
spelling doaj-9ca25e478e9b4432b4fb48e7fe4f4b7a2020-11-25T03:23:10ZengBMCBMC Infectious Diseases1471-23342017-04-0117112110.1186/s12879-017-2355-3Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virusParidhi Gupta0Anuj Sharma1Jing Han2Amy Yang3Manish Bhomia4Barbara Knollmann-Ritschel5Raj K Puri6Radha K Maheshwari7Department of Pathology, Uniformed Services University of the Health SciencesDepartment of Pathology, Uniformed Services University of the Health SciencesDivision of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug AdministrationDivision of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug AdministrationDepartment of Pathology, Uniformed Services University of the Health SciencesDepartment of Pathology, Uniformed Services University of the Health SciencesDivision of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug AdministrationDepartment of Pathology, Uniformed Services University of the Health SciencesAbstract Background Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV causes a bi-phasic illness in mice where primary replication in lymphoid organs is followed by entry into the central nervous system (CNS). The CNS phase of infection is marked by encephalitis and large scale neuronal death ultimately resulting in death. Molecular determinants of VEEV neurovirulence are not well understood. In this study, host gene expression response to highly neurovirulent VEEV (V3000 strain) infection was compared with that of a partially neurovirulent VEEV (V3034 strain) to identify host factors associated with VEEV neurovirulence. Methods Whole genome microarrays were performed to identify the significantly modulated genes. Microarray observations were classified into three categories i.e., genes that were similarly modulated against both V3000 and V3034 infections, and genes that were uniquely modulated in infection with V3034 or V3000. Histologic sections of spleen and brain were evaluated by hematoxylin and eosin stains from all the mice. Results V3000 infection induced a greater degree of pathology in both the spleen and brain tissue of infected mice compared to V3034 infection. Genes commonly modulated in the spleens after V3000 or V3034 infection were associated with innate immune responses, inflammation and antigen presentation, however, V3000 induced a gene response profile that suggests a stronger inflammatory and apoptotic response compared to V3034. In the brain, both the strains of VEEV induced an innate immune response reflected by an upregulation of the genes involved in antigen presentation, interferon response, and inflammation. Similar to the spleen, V3000 was found to induce a stronger inflammatory response than V3034 in terms of induction of pro-inflammatory genes and associated pathways. Ccl2, Ccl5, Ccl6, and Ly6 were uniquely upregulated in V3000 infected mouse brains and correlated with the extensive inflammation observed in the brain. Conclusion The common gene profile identified from V3000 and V3034 exposure can help in understanding a generalized host response to VEEV infection. Inflammatory genes that were uniquely identified in mouse brains with V3000 infection will help in better understanding the lethal neurovirulence of VEEV. Future studies are needed to explore the roles played by the genes identified in VEEV induced encephalitis.http://link.springer.com/article/10.1186/s12879-017-2355-3Venezuelan equine encephalitis virusHost responsesWhole genome microarrayNeurovirulenceV3000V3034
collection DOAJ
language English
format Article
sources DOAJ
author Paridhi Gupta
Anuj Sharma
Jing Han
Amy Yang
Manish Bhomia
Barbara Knollmann-Ritschel
Raj K Puri
Radha K Maheshwari
spellingShingle Paridhi Gupta
Anuj Sharma
Jing Han
Amy Yang
Manish Bhomia
Barbara Knollmann-Ritschel
Raj K Puri
Radha K Maheshwari
Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
BMC Infectious Diseases
Venezuelan equine encephalitis virus
Host responses
Whole genome microarray
Neurovirulence
V3000
V3034
author_facet Paridhi Gupta
Anuj Sharma
Jing Han
Amy Yang
Manish Bhomia
Barbara Knollmann-Ritschel
Raj K Puri
Radha K Maheshwari
author_sort Paridhi Gupta
title Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
title_short Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
title_full Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
title_fullStr Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
title_full_unstemmed Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus
title_sort differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of venezuelan equine encephalitis virus
publisher BMC
series BMC Infectious Diseases
issn 1471-2334
publishDate 2017-04-01
description Abstract Background Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV causes a bi-phasic illness in mice where primary replication in lymphoid organs is followed by entry into the central nervous system (CNS). The CNS phase of infection is marked by encephalitis and large scale neuronal death ultimately resulting in death. Molecular determinants of VEEV neurovirulence are not well understood. In this study, host gene expression response to highly neurovirulent VEEV (V3000 strain) infection was compared with that of a partially neurovirulent VEEV (V3034 strain) to identify host factors associated with VEEV neurovirulence. Methods Whole genome microarrays were performed to identify the significantly modulated genes. Microarray observations were classified into three categories i.e., genes that were similarly modulated against both V3000 and V3034 infections, and genes that were uniquely modulated in infection with V3034 or V3000. Histologic sections of spleen and brain were evaluated by hematoxylin and eosin stains from all the mice. Results V3000 infection induced a greater degree of pathology in both the spleen and brain tissue of infected mice compared to V3034 infection. Genes commonly modulated in the spleens after V3000 or V3034 infection were associated with innate immune responses, inflammation and antigen presentation, however, V3000 induced a gene response profile that suggests a stronger inflammatory and apoptotic response compared to V3034. In the brain, both the strains of VEEV induced an innate immune response reflected by an upregulation of the genes involved in antigen presentation, interferon response, and inflammation. Similar to the spleen, V3000 was found to induce a stronger inflammatory response than V3034 in terms of induction of pro-inflammatory genes and associated pathways. Ccl2, Ccl5, Ccl6, and Ly6 were uniquely upregulated in V3000 infected mouse brains and correlated with the extensive inflammation observed in the brain. Conclusion The common gene profile identified from V3000 and V3034 exposure can help in understanding a generalized host response to VEEV infection. Inflammatory genes that were uniquely identified in mouse brains with V3000 infection will help in better understanding the lethal neurovirulence of VEEV. Future studies are needed to explore the roles played by the genes identified in VEEV induced encephalitis.
topic Venezuelan equine encephalitis virus
Host responses
Whole genome microarray
Neurovirulence
V3000
V3034
url http://link.springer.com/article/10.1186/s12879-017-2355-3
work_keys_str_mv AT paridhigupta differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT anujsharma differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT jinghan differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT amyyang differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT manishbhomia differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT barbaraknollmannritschel differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT rajkpuri differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
AT radhakmaheshwari differentialhostgeneresponsesfrominfectionwithneurovirulentandpartiallyneurovirulentstrainsofvenezuelanequineencephalitisvirus
_version_ 1724607310150500352