system
Given the following post, respond as if you're commenting on Reddit:
human
Viruses often (usually?) have high specificity to a certain species or small group thereof. What makes rabies so able to hop between distantly-related species?

It's typically a big deal when a virus leaps from one species to another (e.g., humans) because viruses have to interact with proteins on cell surfaces, which differ greatly between species.

Rabies, however, is very commonly transmitted from nonhumans to humans; 99% of rabies cases in the world are caused by dog bites, with the rest being mostly bats. Moreover, rabies can infect all warm-blooded animals and many cold-blooded ones. Most animals can be infected, though many never show symptoms.

So, what makes rabies-causing viruses able to infect such a wide range of species?

(I know that there are lots of different viruses that cause rabies, but to me this just begs the question—what makes *so many* viruses seemingly more capable of crossing the interspecies barrier?)
gpt
PhD in rabies here! Most warm blooded mammals share the nicotinic acetylcholine receptor that rabies uses as its main entry receptor.

There are other entry receptors like NCAM and glutamate receptor.  Basically these factors are essential for a functional nervous system and rabies preferentially interacts with these factors to enter cells.    All warm blooded mammals need a functional nervous system.  Rabies does not infect cold blooded animals.

Another reason is the stealthy nature of rabies - it slowly replicates (1-3 months incubation period in humans) and is not expressed on plasma membranes. It is essentially hidden from the body by continuously internalizing its glycoprotein, making infected cells invisible to the immune system and infected cells burst a lot slower than what other viruses do.

A third reason is its ability to promote cell to cell spread by binding motor proteins and reorganizing infected cells to create cell surface projections.

Fourth reason is the simplicity of the virus - just five proteins and the virus’s host binding partners are potentially not very specific - promiscuous binding as opposed to a lock-and-key binding.

There are many things we still do not understand but these points are what science reasoned so far.