Neurotropic Viruses: Trojan for Complex Neurodegenerative Diseases?

Sourish Ghosh^*

National Brain Research Centre, NH-8, Nainwal More, Manesar, 12205, India

*Corresponding Author:

Sourish Ghosh
National Brain Research, Centre
Manesar, Haryana-122051, India
Tel: 91-124-2845225
Fax: 91-124-2338910/28
Email: sourish@nbrc.ac.in

Received February 27, 2015; Accepted April 27, 2014; Published April 29, 2015

Citation: Ghosh S (2015) Neurotropic Viruses: Trojan for Complex Neurodegenerative Diseases? J Neuroinfect Dis 6:173. doi: 10.4172/2314-7326.1000173

Copyright: © 2015 Ghosh S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Neurotropic viruses have been reported to lead to various neurodegenerative diseases [1,2]. The cause and the mechanisms are although undetermined. Various case reports suggest that on the entry of these viruses within the Central Nervous System (CNS) the resident microglial cells become activated [3-5]. Microglial cells on activation lead to release of various chemokines and cytokines which results in bystander killing of the neurons [6]. Viruses often possess a short life cycle within their hosts which after replication to a certain extent gets cleared off by the host immune responses. The major destruction is brought about by the aftermath [7]. This has been reported in cases of various RNA viruses like Japanese Encephalitis Virus (JEV), Chikungunya Virus (CHiKV), Dengueetc [7,8]. On the other hand there are various viruses which prefer to integrate their genome into the host and persist within them. These viruses often get triggered to fast replication when a secondary stimulant or infection attacks the host. Virus induced apoptosis of neuronal cells is one of the major cause of neurodegeneration. The process of apoptosis is often triggered as a host response to various metabolic stress brought about within the cell due to viral replication [9,10]. Hence this uncertainty in gauging the behaviour of each virus makes it difficult to augment a uniform antiviral strategy against these invading neurotropic viruses.

Neurotropic viral infection leading to encephalitis has often been reported to be linked with cognitive and motor disability in the survivors. There are several insights to the question which reasons that these viruses may have some target cells within which they prefer to replicate [11-15]. Hence various studies in animal models have been conducted to surface the underlying mystery of these neurotropic viruses. In case of neurotropic RNA virus full symptomatic animals show familiar symptoms such as hind limb paralysis and decerebrate posturing [16,17]. The movement disabilities often resemble that of Parkinson’s disease. Hence detailed studies on molecular basis of the pathogenesis of neurotropic viruses are required to find answers to the underlying question that whether these viral infections are the sources of sporadic Parkinsons’ disease or other neurodegenerative disease such as Alzheimer’s Disease and Amyolateral Sclerosis Disease (ALS).

The basic question of this article is to whether the neurotropic infections may form root cause for many of the sporadic cases of neurodegenerations. If we put the molecular studies conducted to identify the common mechanism of the neurodegenerative disease under the magnifying glass a common trend is often observed. All these neurodegenerative diseases bring about the neuronal death through a common mechanism of neuronal apoptosis [18,19]. In most of the neurodegenerative diseases there are primarily two root causes one happens to be genetic another happens to be sporadic. In this report we are concerned about sporadic cases since neurotropic virus attack in early stage of life may stimulate the onset of these neurodegenerations [20,21]. In sporadic cases of various neurodegenerative diseases phenomena like oxidative stress holds an important cue [22,23]. Neurotropic viruses bring about neurodegeneration stimulating oxidative stress leading to processes such as endoplasmic reticulum stress (ER stress), mitochondrial stress. These stress induction and starting of the process of neurodegeneration at some early point of life by infection of neurotropic viruses may have a persistent effect in the victim host. It can be hypothesized that molecules pertaining to the same pathway may undergo some mutations which through the course of time influence the onset of various neurodegenerative diseases.

In conclusion, to address this type of complex problem investigators need to understand each phases of these diseases along with their underlying molecular events. With the advent of various branches of modern day interdisciplinary science concepts like systems biology along with other omics branch of studies need to be integrated to understand and “fish out” the pivotal molecules which plays key role in the neurodegenerative diseases. We have to remember that targeting viral genome which is highly susceptible to mutations as anti-viral therapies are outdated approach. Anti-viral therapies to neurotropic viruses must be targeted towards a stronger “host response” and thus cut out the chances of the aftermath of viral infections leading to severe complex neurodegenerative diseases.

Acknowledgements

The lab is funded by a grant from the Department of Biotechnology (BT/ PR7907/MED/29/702/2013) awarded to Dr.AnirbanBasu. I would like to thank Mrs. SripanaNath for final editing of the manuscript.

References

1. Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, et al. (2014) Inflammation in neurodegenerative diseases--an update. Immunology 142: 151-166.
2. Zhou L, Miranda-Saksena M, Saksena NK (2013) Viruses and neurodegeneration. Virol J 10: 172.
3. Ghoshal A, Das S, Ghosh S, Mishra MK, Sharma V, et al. (2007) Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55: 483-496.
4. Mishra MK, Basu A (2008) Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. J Neurochem 105: 1582-1595.
5. Swarup V, Ghosh J, Mishra MK, Basu A (2008) Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan. J Antimicrob Chemother 61: 679-688.
6. Kaushik DK, Gupta M, Kumawat KL, Basu A (2012) NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. PLoS One 7: e32270.
7. Das S, Basu A (2008) Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation. J Neurochem 106: 1624-1636.
8. Leis AA, Stokic DS (2005) Neuromuscular Manifestations of Human West Nile Virus Infection. Curr Treat Options Neurol 7: 15-22.
9. Ghosh S, Dutta K, Basu A (2013) Chandipura virus induces neuronal death through Fas-mediated extrinsic apoptotic pathway. J Virol 87: 12398-12406.
10. Yang KD, Yeh WT, Chen RF, Chuon HL, Tsai HP, et al. (2004) A model to study neurotropism and persistency of Japanese encephalitis virus infection in human neuroblastoma cells and leukocytes. J Gen Virol 85: 635-642.
11. CAMPBELL B (1946) Physiological effects of chromatolysis and of virus invasion of motor neurons. Anat Rec 94: 451.
12. Darman J, Backovic S, Dike S, Maragakis NJ, Krishnan C, et al. (2004) Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. J Neurosci 24: 7566-7575.
13. Johnson RT (1982) Selective vulnerability of neural cells to viral infections. Adv Neurol 36: 331-337.
14. Kerr DA, Nery JP, Traystman RJ, Chau BN, Hardwick JM (2000) Survival motor neuron protein modulates neuron-specific apoptosis. Proc Natl Acad Sci U S A 97: 13312-13317.
15. Sola P, Bedin R, Casoni F, Barozzi P, Mandrioli J, et al. (2002) New insights into the viral theory of amyotrophic lateral sclerosis: study on the possible role of Kaposi's sarcoma-associated virus/human herpesvirus 8. Eur Neurol 47: 108-112.
16. Brison E, Jacomy H, Desforges M ,Talbot PJ (2011) Glutamate excitotoxicity is involved in the induction of paralysis in mice after infection by a human coronavirus with a single point mutation in its spike protein. J Virol 85: 12464-12473.
17. Jolicoeur P, DesGroseillers L (1985) Neurotropic Cas-BR-E murine leukemia virus harbors several determinants of leukemogenicity mapping in different regions of the genome. J Virol 56: 639-643.
18. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, et al. (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441: 1162-1166.
19. Gamblin TC, Chen F, Zambrano A, Abraha A, Lagalwar S, et al. (2003) Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc Natl Acad Sci U S A 100: 10032-10037.
20. Clark LN, Afridi S, Mejia-Santana H, Harris J, Louis ED, et al. (2004) Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations. Mov Disord 19: 796-800.
21. Bertram L, Mullin K, Parkinson M, Hsiao M, Moscarillo TJ, et al. (2007) Is alpha-T catenin (VR22) an Alzheimer's disease risk gene? J Med Genet 44: e63.
22. Nunomura A, Moreira PI, Lee HG, Zhu X, Castellani RJ, et al. (2007) Neuronal death and survival under oxidative stress in Alzheimer and Parkinson diseases. CNS Neurol Disord Drug Targets 6: 411-423.
23. Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, et al. (2004) Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem 279: 13256-13264.