Chronic Progressive Deficits in Neuron Size, Density and Number in the Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus

Overview

Journal Brain Pathol

Date 2011 Mar 5

PMID 21371157

Citations 6

Authors

Sandor Dosa

Karla Castellanos

Sarolta Bacsa

Eva Gagyi

S Krisztian Kovacs

Klara Valyi-Nagy

Deepak Shukla

Terence S Dermody

Tibor Valyi-Nagy

Affiliations

Soon will be listed here.

Abstract

Numerous epidemiological studies have proposed a link between herpes simplex virus (HSV) infection and several common chronic neuropsychiatric and neurodegenerative diseases. Experimental HSV infection of mice can lead to chronic behavioral and neurological deficits and chronic pain. While neuron injury and loss are well-documented consequences of the acute phase of infection, the pathologic consequences of latent HSV infection are poorly understood. To determine whether latent HSV infection can cause neuronal injury in mice, trigeminal ganglia (TG) derived from adult BALB/c mice 1, 12 and 31 weeks after corneal HSV type 1 (HSV-1) inoculation were analyzed for evidence of productive or latent HSV-1 infection, inflammation and changes in neuron size, density and number. We found that latent HSV-1 infection between 12 and 31 weeks after corneal virus inoculation was associated with inflammation and progressive deficits in mean neuron diameter, neuronal nucleus diameter, neuron density and neuron number in the TG relative to mock-infected controls. The extent of neuronal injury during latent infection correlated with the extent of inflammation. These studies demonstrate that latent HSV infection is associated with progressive neuronal pathology and may lead to a better understanding of the role of HSV infections in chronic neurological diseases.

Citing Articles

Disrupting Neurons and Glial Cells Oneness in the Brain-The Possible Causal Role of Herpes Simplex Virus Type 1 (HSV-1) in Alzheimer's Disease.

Mielcarska M, Skowronska K, Wyzewski Z, Toka F Int J Mol Sci. 2022; 23(1).

PMID: 35008671 PMC: 8745046. DOI: 10.3390/ijms23010242.

Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

Brun P, Qesari M, Marconi P, Kotsafti A, Porzionato A, Macchi V Front Cell Infect Microbiol. 2018; 8:74.

PMID: 29600197 PMC: 5862801. DOI: 10.3389/fcimb.2018.00074.

Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease.

Jiang Y, Patel C, Manivanh R, North B, Backes I, Posner D mBio. 2017; 8(4).

PMID: 28679745 PMC: 5573671. DOI: 10.1128/mBio.00678-17.

The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features.

Fan S, Cai H, Xu X, Feng M, Wang L, Liao Y Viruses. 2017; 9(2).

PMID: 28146109 PMC: 5332945. DOI: 10.3390/v9020026.

Ocular and neural distribution of feline herpesvirus-1 during active and latent experimental infection in cats.

Townsend W, Jacobi S, Tai S, Kiupel M, Wise A, Maes R BMC Vet Res. 2013; 9:185.

PMID: 24053192 PMC: 4016492. DOI: 10.1186/1746-6148-9-185.

References

Khanna K, Bonneau R, Kinchington P, Hendricks R . Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity. 2003; 18(5):593-603. PMC: 2871305. DOI: 10.1016/s1074-7613(03)00112-2. View

Baringer J, Swoveland P . Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973; 288(13):648-50. DOI: 10.1056/NEJM197303292881303. View

Fraser N, LAWRENCE W, WROBLEWSKA Z, Gilden D, KOPROWSKI H . Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci U S A. 1981; 78(10):6461-5. PMC: 349059. DOI: 10.1073/pnas.78.10.6461. View

Yolken R . Viruses and schizophrenia: a focus on herpes simplex virus. Herpes. 2004; 11 Suppl 2:83A-88A. View

Brown S, Ritchie D . Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. J Gen Virol. 1973; 18(3):329-46. DOI: 10.1099/0022-1317-18-3-329. View

Knickelbein J, Khanna K, Yee M, Baty C, Kinchington P, Hendricks R . Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science. 2008; 322(5899):268-71. PMC: 2680315. DOI: 10.1126/science.1164164. View

Simpson-Holley M, Colgrove R, Nalepa G, Harper J, Knipe D . Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection. J Virol. 2005; 79(20):12840-51. PMC: 1235858. DOI: 10.1128/JVI.79.20.12840-12851.2005. View

Croen K, Ostrove J, Dragovic L, Straus S . Patterns of gene expression and sites of latency in human nerve ganglia are different for varicella-zoster and herpes simplex viruses. Proc Natl Acad Sci U S A. 1988; 85(24):9773-7. PMC: 282863. DOI: 10.1073/pnas.85.24.9773. View

Shimeld C, Whiteland J, Nicholls S, Grinfeld E, Easty D, Gao H . Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1. J Neuroimmunol. 1995; 61(1):7-16. DOI: 10.1016/0165-5728(95)00068-d. View

10.

Takasaki I, Nojima H, Shiraki K, Sugimoto Y, Ichikawa A, Ushikubi F . Involvement of cyclooxygenase-2 and EP3 prostaglandin receptor in acute herpetic but not postherpetic pain in mice. Neuropharmacology. 2005; 49(3):283-92. DOI: 10.1016/j.neuropharm.2004.12.025. View

11.

Devor M, Govrin-Lippmann R, Frank I, Raber P . Proliferation of primary sensory neurons in adult rat dorsal root ganglion and the kinetics of retrograde cell loss after sciatic nerve section. Somatosens Res. 1985; 3(2):139-67. DOI: 10.3109/07367228509144581. View

12.

Valyi-Nagy T, Gesser R, Raengsakulrach B, Deshmane S, Randazzo B, Dillner A . A thymidine kinase-negative HSV-1 strain establishes a persistent infection in SCID mice that features uncontrolled peripheral replication but only marginal nervous system involvement. Virology. 1994; 199(2):484-90. DOI: 10.1006/viro.1994.1150. View

13.

Feldman L, Ellison A, Voytek C, Yang L, Krause P, Margolis T . Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci U S A. 2002; 99(2):978-83. PMC: 117416. DOI: 10.1073/pnas.022301899. View

14.

Kramer M, Cook W, Roth F, Zhu J, Holman H, Knipe D . Latent herpes simplex virus infection of sensory neurons alters neuronal gene expression. J Virol. 2003; 77(17):9533-41. PMC: 187408. DOI: 10.1128/jvi.77.17.9533-9541.2003. View

15.

Cantin E, Hinton D, Chen J, Openshaw H . Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. J Virol. 1995; 69(8):4898-905. PMC: 189304. DOI: 10.1128/JVI.69.8.4898-4905.1995. View

16.

Schretlen D, Vannorsdall T, Winicki J, Mushtaq Y, Hikida T, Sawa A . Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia. Schizophr Res. 2010; 118(1-3):224-31. DOI: 10.1016/j.schres.2010.01.008. View

17.

Henken D, Goldstein M, Martin J . Herpes simplex virus type-2 infection by a footpad route results in neuronal death in mouse spinal ganglia. J Neurol Sci. 1993; 115(2):177-83. DOI: 10.1016/0022-510x(93)90222-k. View

18.

Armien A, Hu S, Little M, Robinson N, Lokensgard J, Low W . Chronic cortical and subcortical pathology with associated neurological deficits ensuing experimental herpes encephalitis. Brain Pathol. 2009; 20(4):738-50. PMC: 2895975. DOI: 10.1111/j.1750-3639.2009.00354.x. View

19.

Valyi-Nagy T, Sheth V, Clement C, Tiwari V, Scanlan P, Kavouras J . Herpes simplex virus entry receptor nectin-1 is widely expressed in the murine eye. Curr Eye Res. 2004; 29(4-5):303-9. DOI: 10.1080/02713680490516756. View

20.

Ciaroni S, Cecchini T, Cuppini R, Ferri P, Ambrogini P, Bruno C . Are there proliferating neuronal precursors in adult rat dorsal root ganglia?. Neurosci Lett. 2000; 281(1):69-71. DOI: 10.1016/s0304-3940(00)00785-0. View