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Neurotropic viruses have been reported to lead to various neurodegenerative diseases. 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. Microglial cells on activation lead to release of various chemokines and cytokines which results in bystander killing of the neurons. 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. This has been reported in cases of various RNA viruses like Japanese Encephalitis Virus (JEV), Chikungunya Virus (CHiKV), Dengueetc. 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. Hence this uncertainty in gauging the behaviour of each virus makes it difficult to augment a uniform antiviral strategy against these invading neurotropic viruses.