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Published in: Journal of NeuroVirology 3/2019

01-06-2019 | Herpes Virus

The recruitment of peripheral blood leukocytes to the brain is delayed in susceptible BALB/c compared to resistant C57BL/6 mice during herpes simplex virus encephalitis

Authors: Coraline Canivet, Olus Uyar, Chantal Rhéaume, Jocelyne Piret, Guy Boivin

Published in: Journal of NeuroVirology | Issue 3/2019

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Abstract

The cerebral immune response induced by herpes simplex virus (HSV) encephalitis (HSE) was evaluated in susceptible BALB/c and resistant C57BL/6 mice. BALB/c and C57BL/6 (named C57BL/6-high) mice were respectively infected intranasally with 1 × 103 and 5 × 105 plaque-forming units (PFUs) of HSV-1. C57BL/6 mice (named C57BL/6-low) infected with a low inoculum (1 × 103 PFUs) of HSV-1 were tested in parallel. Mice were monitored for weight loss, sickness signs, and survival for 21 days. The viral load, infectious titers, cytokine/chemokine levels, and peripheral leukocyte infiltration were determined in brain homogenates on days 0 (non-infected), 4, 6, and 8 post-infection (p.i.) by qPCR, plaque assay, ELISA/Luminex™, and flow cytometry, respectively. Our results showed that the mortality of BALB/c mice (67%) was higher compared to those of C57BL/6-low (0%; P ≤ 0.01) and C57BL/6-high (20%; P ≤ 0.05) animals. This higher mortality was associated with increased infectious titers and cytokine/chemokine levels in the brains of BALB/c compared to C57BL/6 mice. Recruitment of inflammatory monocytes, dendritic cells, natural killer, and natural killer T cells to the brain was higher in C57BL/6-high compared to BALB/c animals on day 4 p.i. Infiltration of inflammatory monocytes and T cells in the brain of BALB/c mice was seen on day 6 p.i. Our data suggest that a rapid, sustained, and coordinated recruitment of peripheral leukocytes to the brain of C57BL/6-high mice results in an effective control of viral replication and inflammation whereas the delayed infiltration of immune cells in the brain of BALB/c mice was associated with an exacerbated inflammatory response during HSE.
Literature
go back to reference Boivin G, Goyette N, Sergerie Y, Keays S, Booth T (2006) Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis. J Clin Virol 37:248–251CrossRefPubMed Boivin G, Goyette N, Sergerie Y, Keays S, Booth T (2006) Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis. J Clin Virol 37:248–251CrossRefPubMed
go back to reference Ghiasi H, Cai S, Perng GC, Nesburn AB, Wechsler SL (2000) The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection. Antivir Res 45:33–45CrossRefPubMed Ghiasi H, Cai S, Perng GC, Nesburn AB, Wechsler SL (2000) The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection. Antivir Res 45:33–45CrossRefPubMed
go back to reference Habu S, Akamatsu K, Tamaoki N, Okumura K (1984) In vivo significance of NK cell on resistance against virus (HSV-1) infections in mice. J Immunol 133:2743–2747PubMed Habu S, Akamatsu K, Tamaoki N, Okumura K (1984) In vivo significance of NK cell on resistance against virus (HSV-1) infections in mice. J Immunol 133:2743–2747PubMed
go back to reference Kastrukoff LF, Lau AS, Takei F, Smyth MJ, Jones CM, Clarke SR, Carbone FR (2010) Redundancy in the immune system restricts the spread of HSV-1 in the central nervous system (CNS) of C57BL/6 mice. Virology 400:248–258CrossRefPubMed Kastrukoff LF, Lau AS, Takei F, Smyth MJ, Jones CM, Clarke SR, Carbone FR (2010) Redundancy in the immune system restricts the spread of HSV-1 in the central nervous system (CNS) of C57BL/6 mice. Virology 400:248–258CrossRefPubMed
go back to reference Lokensgard JR, Hu S, Sheng W, vanOijen M, Cox D, Cheeran MC, Peterson PK (2001) Robust expression of TNF-alpha, IL-1beta, RANTES, and IP-10 by human microglial cells during nonproductive infection with herpes simplex virus. J NeuroVirol 7:208–219 Lokensgard JR, Hu S, Sheng W, vanOijen M, Cox D, Cheeran MC, Peterson PK (2001) Robust expression of TNF-alpha, IL-1beta, RANTES, and IP-10 by human microglial cells during nonproductive infection with herpes simplex virus. J NeuroVirol 7:208–219
go back to reference Lopez C (1975) Genetics of natural resistance to herpesvirus infections in mice. Nature 258:152–153CrossRefPubMed Lopez C (1975) Genetics of natural resistance to herpesvirus infections in mice. Nature 258:152–153CrossRefPubMed
go back to reference Lundberg P, Welander P, Openshaw H, Nalbandian C, Edwards C, Moldawer L, Cantin E (2003) A locus on mouse chromosome 6 that determines resistance to herpes simplex virus also influences reactivation, while an unlinked locus augments resistance of female mice. J Virol 77:11661–11673CrossRefPubMedPubMedCentral Lundberg P, Welander P, Openshaw H, Nalbandian C, Edwards C, Moldawer L, Cantin E (2003) A locus on mouse chromosome 6 that determines resistance to herpes simplex virus also influences reactivation, while an unlinked locus augments resistance of female mice. J Virol 77:11661–11673CrossRefPubMedPubMedCentral
go back to reference Lundberg P, Welander PV, Edwards CK 3rd, van Rooijen N, Cantin E (2007) Tumor necrosis factor (TNF) protects resistant C57BL/6 mice against herpes simplex virus-induced encephalitis independently of signaling via TNF receptor 1 or 2. J Virol 81:1451–1460CrossRefPubMed Lundberg P, Welander PV, Edwards CK 3rd, van Rooijen N, Cantin E (2007) Tumor necrosis factor (TNF) protects resistant C57BL/6 mice against herpes simplex virus-induced encephalitis independently of signaling via TNF receptor 1 or 2. J Virol 81:1451–1460CrossRefPubMed
go back to reference Marques CP, Hu S, Sheng W, Lokensgard JR (2006) Microglial cells initiate vigorous yet non-protective immune responses during HSV-1 brain infection. Virus Res 121:1–10CrossRefPubMed Marques CP, Hu S, Sheng W, Lokensgard JR (2006) Microglial cells initiate vigorous yet non-protective immune responses during HSV-1 brain infection. Virus Res 121:1–10CrossRefPubMed
go back to reference Marques CP, Cheeran MC, Palmquist JM, Hu S, Urban SL, Lokensgard JR (2008) Prolonged microglial cell activation and lymphocyte infiltration following experimental herpes encephalitis. J Immunol 181:6417–6426CrossRefPubMedPubMedCentral Marques CP, Cheeran MC, Palmquist JM, Hu S, Urban SL, Lokensgard JR (2008) Prolonged microglial cell activation and lymphocyte infiltration following experimental herpes encephalitis. J Immunol 181:6417–6426CrossRefPubMedPubMedCentral
go back to reference Paludan SR, Melchjorsen J, Malmgaard L, Mogensen SC (2002) Expression of genes for cytokines and cytokine-related functions in leukocytes infected with Herpes simplex virus: comparison between resistant and susceptible mouse strains. Eur Cytokine Netw 13:306–316PubMed Paludan SR, Melchjorsen J, Malmgaard L, Mogensen SC (2002) Expression of genes for cytokines and cytokine-related functions in leukocytes infected with Herpes simplex virus: comparison between resistant and susceptible mouse strains. Eur Cytokine Netw 13:306–316PubMed
go back to reference Pepose JS, Whittum-Hudson JA (1987) An immunogenetic analysis of resistance to herpes simplex virus retinitis in inbred strains of mice. Invest Ophthalmol Vis Sci 28:1549–1552PubMed Pepose JS, Whittum-Hudson JA (1987) An immunogenetic analysis of resistance to herpes simplex virus retinitis in inbred strains of mice. Invest Ophthalmol Vis Sci 28:1549–1552PubMed
go back to reference Pereira RA, Scalzo A, Simmons A (2001) Cutting edge: a NK complex-linked locus governs acute versus latent herpes simplex virus infection of neurons. J Immunol 166:5869–5873CrossRefPubMed Pereira RA, Scalzo A, Simmons A (2001) Cutting edge: a NK complex-linked locus governs acute versus latent herpes simplex virus infection of neurons. J Immunol 166:5869–5873CrossRefPubMed
go back to reference Rozenberg F, Deback C, Agut H (2011) Herpes simplex encephalitis : from virus to therapy. Infect Disord Drug Targets 11:235–250CrossRefPubMed Rozenberg F, Deback C, Agut H (2011) Herpes simplex encephalitis : from virus to therapy. Infect Disord Drug Targets 11:235–250CrossRefPubMed
go back to reference Sergerie Y, Boivin G, Gosselin D, Rivest S (2007) Delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice. J Infect Dis 195:817–825CrossRefPubMed Sergerie Y, Boivin G, Gosselin D, Rivest S (2007) Delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice. J Infect Dis 195:817–825CrossRefPubMed
go back to reference Tyler KL (2004) Update on herpes simplex encephalitis. Rev Neurol Dis 1:169–178PubMed Tyler KL (2004) Update on herpes simplex encephalitis. Rev Neurol Dis 1:169–178PubMed
go back to reference Wuest TR, Carr DJ (2008) Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection. J Immunol 181:7985–7993CrossRefPubMedPubMedCentral Wuest TR, Carr DJ (2008) Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection. J Immunol 181:7985–7993CrossRefPubMedPubMedCentral
go back to reference Zawatzky R, Gresser I, DeMaeyer E, Kirchner H (1982) The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1. J Infect Dis 146:405–410CrossRefPubMed Zawatzky R, Gresser I, DeMaeyer E, Kirchner H (1982) The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1. J Infect Dis 146:405–410CrossRefPubMed
Metadata
Title
The recruitment of peripheral blood leukocytes to the brain is delayed in susceptible BALB/c compared to resistant C57BL/6 mice during herpes simplex virus encephalitis
Authors
Coraline Canivet
Olus Uyar
Chantal Rhéaume
Jocelyne Piret
Guy Boivin
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology / Issue 3/2019
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-019-00730-5

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