Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus

Kimberly K. Roberts, Terence E. Hill, Melissa N. Davis, Michael R. Holbrook, Alexander Freiberg

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.

Original languageEnglish (US)
Pages (from-to)1651-1663
Number of pages13
JournalJournal of General Virology
Volume96
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Rift Valley fever virus
Macrophages
Cytokines
Antiviral Agents
Infection
Virus Diseases
Virulence
Phlebovirus
Bunyaviridae
Viral Structures
Interferon Type I
Interleukins
Livestock
Adaptive Immunity
Chemokines
Innate Immunity
Dendritic Cells
Genes

ASJC Scopus subject areas

  • Virology

Cite this

Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus. / Roberts, Kimberly K.; Hill, Terence E.; Davis, Melissa N.; Holbrook, Michael R.; Freiberg, Alexander.

In: Journal of General Virology, Vol. 96, No. 7, 01.07.2015, p. 1651-1663.

Research output: Contribution to journalArticle

Roberts, Kimberly K. ; Hill, Terence E. ; Davis, Melissa N. ; Holbrook, Michael R. ; Freiberg, Alexander. / Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus. In: Journal of General Virology. 2015 ; Vol. 96, No. 7. pp. 1651-1663.
@article{2e697f295acb495997e72878b1bf81bf,
title = "Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus",
abstract = "Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.",
author = "Roberts, {Kimberly K.} and Hill, {Terence E.} and Davis, {Melissa N.} and Holbrook, {Michael R.} and Alexander Freiberg",
year = "2015",
month = "7",
day = "1",
doi = "10.1099/vir.0.000119",
language = "English (US)",
volume = "96",
pages = "1651--1663",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Society for General Microbiology",
number = "7",

}

TY - JOUR

T1 - Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus

AU - Roberts, Kimberly K.

AU - Hill, Terence E.

AU - Davis, Melissa N.

AU - Holbrook, Michael R.

AU - Freiberg, Alexander

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.

AB - Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.

UR - http://www.scopus.com/inward/record.url?scp=84938310591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938310591&partnerID=8YFLogxK

U2 - 10.1099/vir.0.000119

DO - 10.1099/vir.0.000119

M3 - Article

C2 - 25759029

AN - SCOPUS:84938310591

VL - 96

SP - 1651

EP - 1663

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 7

ER -