TY - JOUR
T1 - Robust expression of TNF-α, IL-1β, RANTES, and IP-10 by human microglial cells during nonproductive infection with herpes simplex virus
AU - Lokensgard, J. R.
AU - Hu, S.
AU - Sheng, W.
AU - vanOijen, M.
AU - Cox, D.
AU - Cheeran, M. C J
AU - Peterson, P. K.
PY - 2001
Y1 - 2001
N2 - Cytokine (TNF-α/β, IL-1β, IL-6, IL-18, IL-10, and IFN-α/β/γ) and chemokine (IL-8, IP-10, MCP-1, MIP-1α/β, and RANTES) production during herpes simplex virus (HSV) 1 infection of human brain cells was examined. Primary astrocytes as well as neurons were found to support HSV replication, but neither of these fully permissive cell types produced cytokines or chemokines in response to HSV. In contrast, microglia did not support extensive viral replication; however, ICP4 was detected by immunochemical staining, demonstrating these cells were infected. Late viral protein (nucleocapsid antigen) was detected in <10% of infected microglial cells. Microglia responded to nonpermissive viral infection by producing considerable amounts of TNF-α, IL-1β, IP-10, and RANTES, together with smaller amounts of IL-6, IL-8, and MIP-1α as detected by RPA and ELISA. Surprisingly, no interferons (α, β, or γ) were detected in response to viral infection. Pretreatment of fully permissive astrocytes with TNF-α prior to infection with HSV was found to dramatically inhibit replication, resulting in a 14-fold reduction of viral titer. In contrast, pretreatment of astrocytes with IL-1β had little effect on viral replication. When added to neuronal cultures, exogenous TNF-α or IL-1β did not suppress subsequent HSV replication. Exogenously added IP-10 inhibited HSV replication in neurons (with a 32-fold reduction in viral titer), however, similar IP-10 treatment did not affect viral replication in astrocytes. These results suggest that IP-10 possesses direct antiviral activity in neurons and support a role for microglia in both antiviral defense of the brain as well as amplification of immune responses during neuroinflammation.
AB - Cytokine (TNF-α/β, IL-1β, IL-6, IL-18, IL-10, and IFN-α/β/γ) and chemokine (IL-8, IP-10, MCP-1, MIP-1α/β, and RANTES) production during herpes simplex virus (HSV) 1 infection of human brain cells was examined. Primary astrocytes as well as neurons were found to support HSV replication, but neither of these fully permissive cell types produced cytokines or chemokines in response to HSV. In contrast, microglia did not support extensive viral replication; however, ICP4 was detected by immunochemical staining, demonstrating these cells were infected. Late viral protein (nucleocapsid antigen) was detected in <10% of infected microglial cells. Microglia responded to nonpermissive viral infection by producing considerable amounts of TNF-α, IL-1β, IP-10, and RANTES, together with smaller amounts of IL-6, IL-8, and MIP-1α as detected by RPA and ELISA. Surprisingly, no interferons (α, β, or γ) were detected in response to viral infection. Pretreatment of fully permissive astrocytes with TNF-α prior to infection with HSV was found to dramatically inhibit replication, resulting in a 14-fold reduction of viral titer. In contrast, pretreatment of astrocytes with IL-1β had little effect on viral replication. When added to neuronal cultures, exogenous TNF-α or IL-1β did not suppress subsequent HSV replication. Exogenously added IP-10 inhibited HSV replication in neurons (with a 32-fold reduction in viral titer), however, similar IP-10 treatment did not affect viral replication in astrocytes. These results suggest that IP-10 possesses direct antiviral activity in neurons and support a role for microglia in both antiviral defense of the brain as well as amplification of immune responses during neuroinflammation.
KW - Cytokines
KW - Encephalitis
KW - Microglia
UR - http://www.scopus.com/inward/record.url?scp=0034922931&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034922931&partnerID=8YFLogxK
U2 - 10.1080/13550280152403254
DO - 10.1080/13550280152403254
M3 - Article
C2 - 11517395
AN - SCOPUS:0034922931
SN - 1355-0284
VL - 7
SP - 208
EP - 219
JO - Journal of neurovirology
JF - Journal of neurovirology
IS - 3
ER -