Neurotropic Viruses: An insight into their movement

The rabies virus moves differently compared to other neuron-invading viruses and its journey can be blocked by a drug commonly used to treat amoebic dysentery.

It is when the immune system is compromised that most viruses infect the nervous system accidentally. But there are certain viruses called the neurotropic viruses that target neurons as part of their normal infectious cycle. The rabies virus is an example to this where the virus is transmitted when an infected animal bites a host. It then spreads into the end terminals of motor neurons innervating the muscle and travels along the neurons' long axon fibres to the neuronal cell bodies, throughout the central nervous system and into the salivary glands, where it can be  transmitted to other hosts.

Alpha herpes viruses, such as herpes simplex viruses, also enter peripheral nerve terminals and move along axons to the neuronal cell body, where they can lie dormant. Alpha Herpes viruses engage the neuronal transport machinery by stimulating protein synthesis at infected nerve terminals. Transport of the viral particles to the cell body can therefore be blocked by drugs that inhibit protein synthesis, as well as by cellular antiviral proteins called interferons.

In contrast to alpha herpes virus infections, the interferon’s had no effect on rabies virus transport, perhaps because, until it reaches the neuronal cell body, the rabies virus hides out inside cellular structures called endosomes.

Transport of these viruses to the neuronal cell body is an active process which completely relies on the neuron's own motor proteins and microtubule tracks. Infection cannot start until and unless the viral particles engage this machinery for efficient transport in the axons Neurons were infected with a virulent strain of the virus tagged with a red fluorescent protein, allowing the observation of viral transport in real time by live-cell fluorescence microscopy to determine how the rabies virus engages the neuronal transport machinery.

Increased protein synthesis was also not detected in axons upon rabies virus infection. But, it was seen that a protein synthesis inhibitor called emetine efficiently blocked rabies virus transport to the cell body. The movement or mobility of endosomes with the virus was either completely blocked, or was only able to move short distances at slower speeds. Other protein synthesis inhibitors did not block rabies virus transport, which suggest that emetine functions by inhibiting a different process in infected neurons.

Emetine has been used to treat amoebic dysentery and in laboratory it is widely used to inhibit protein synthesis but there are recent reports indicating that emetine has anti-viral effects that are independent of protein synthesis inhibition. This study shows that this drug can inhibit rabies virus invasion of the nervous system through a novel mechanism that hasn't been reported before. This study both advances and complicates our understanding of how neurotropic viruses make their way from the axon terminus to the cell body. The next step would be to figure out how emetine disrupts rabies virus transport in axons