A neurotropic virus is a virus which capable of infecting nerve cells.

Herpes simplex virus (HSV) has low neuroinvasivesess and high neurovirulence. HSV is transmitted in vesicle fluid, saliva and vaginal secretions. So the site of infection determines the disease - "mixing and matching of mucous membranes".

Source: Murray 2013, Medical Microbiology.

Why is herpes virus neurotropic?

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    $\begingroup$ What's the difference between neurovirulence and neurovasiveness $\endgroup$ Jul 21, 2017 at 12:17

2 Answers 2


Simply because it has neurotropic receptors. Why did acquiring these receptors seem evolutionarily advantageous? Well the immune system doesn't target nerve cells for destruction as well. There are few if any white blood cells in the CSF within which the neurones are bathed. The immune system is about protecting against damage, it doesn't care as much if a virus doesn't cause damage as it isn't geared to respond as well if that's the case.


1/How Herpes does it:

Quote: << HSV... can enter the Peripheral Nervous System by binding to receptors on axon termini of sensory and autonomic neurons, which respectively convey sensory and visceral information. Most alpha herpesviruses use this route to enter the PNS and establish a life-long persistent infection [3].

Human alpha herpesviruses include herpes simplex type-1 (HSV-1), HSV-2. Well-studied animal alpha herpesviruses include pseudorabies virus (PRV) and bovine herpes virus (BHV). The cellular adhesion molecule, Nectin-1, is a major neuronal receptor for these viruses. Alpha herpesvirus particles enter sensory nerve endings by membrane fusion, and engage dynein motors for retrograde transport to the neuronal cell body or soma [4]. The capsids then dock at the nuclear pore and the viral DNA is instilled in the nucleus where an acute or a quiescent, latent infection is established. These viruses are unique in maintaining quiescent infections in the PNS neurons of their hosts. This quiescent state can be reversed by certain stress stimuli, which results in the production of large numbers of progeny in a relatively short period of time (1–2 days) [5]. Despite the direct synaptic connection of PNS neurons to the CNS, spread of alpha herpesvirus infection to the CNS is rare, but debilitating, in natural hosts [3]. Alpha herpesvirus trafficking, latency and reactivation is further reviewed in the following sections. Quite complex paper that outlines the nerve invasion strategies of majore nervous system virii, even rabies, polio, smallpox: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647473/ >> end quote

2/Why Herpes has a particular advantage:

HSV has a statistically efficient infection and dormancy habit(near 100% of adults, 60% of them have HSV-1) It has the particular ability to achieve suspended animation, blocking the nerve immune response with special RNA strands, even if is detected there, inside nerves, it stays very benign/docile, it can stay latent in a host for very many years...

The last thing a virus needs is a dead end host, it's main objective is to spread and maintan as widespread a host population as it can. When we’re healthy, HSV-1 snoozes inside our neurons, secluded from drugs and the immune system. the latency is controlled by dissemination RNA strands that control the host nerve cells ability at apoptosis, or programmed cell death due to infection, so it can live as a reservoir of virii inside a cell for many years.

Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. https://www.ncbi.nlm.nih.gov/pubmed/24916030

Red blood cells and other cells don't live as long as nerve cells: Most neurons are formed before birth and survive for the lifetime of the individual, so their lifespan is the same as that of the body. (for peripheral nervous cells the figure is also impressive, they can even grow back when damaged).

When it breaks out, it has an efficient vector of transmission which more controlled and less alarming than smallpox or more virulent virii, and enable the hosts to stay associated with is group during and outbreak, rather than causing the host to become an outcast. Animals instinctively take fright of pathogen symptoms and can distance themselves from shared foods, objects, and periphery of a symptomatic host. Herpes only causes very minor symptoms.

The transfer of viral particles between individuals, as the production of viral particles does not necessarily require any noticeable damage to the host. HSV achieves this using a very fine tuned balance of latency or lyse/cell outbreak, which is when it explodes host cells and causes an immune response that sheds the virii at the surface.

The RNA latency control mechanism is highly evolved and fine tuned to control the nerve cell, there has been recent research about it, it's here: https://en.wikipedia.org/wiki/HHV_Latency_Associated_Transcript this means that nearly 100% of the adult population is infected with the herpesviridae family of virii: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809354/

Other virii have different survival strategies, like cold and flue virii, which flee to the epithelial cells of the host in order to not decimate the host population, as if to flee the host by going to the surface of the host, because they don't have much control over their own virulence in through other methods, they don't know if they are being virulent or not. ... Other than that, HSV automatically explodes epithelial cells, and it's ability to enter and hide inside nerve cells is it's strength. it's very complex how it does that, HSV is a very adapted, sleek, efficient virus.

I can't prove this theory, but it's possible that this HSV can confer added robustness to the host population, by keeping it's nerve immune response tip-top through the generations, and make it more able to combat other nerve virii like H1N1. Sometimes it's difficult to think that a virus that has been with use for millions of years is not part of of the body itself.


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