Herpesviruses steal one cell’s protein, use it to infect another

One of many defining options of viruses is that they depend on host proteins as a way to reproduce. A number cell will typically copy viral genes into RNAs after which translate these RNAs into proteins, for instance. Usually, a mature virus that is able to unfold to a different cell has little greater than viral proteins, the virus’s genetic materials, and possibly among the host’s membrane. It would not want a lot else; all of the proteins it wants to breed additional must be current within the subsequent cell it infects.

However some information launched this week might have discovered an exception to this sample. Members of the herpesvirus household seem to latch on to a protein within the first cell they infect after which carry this protein together with them to the following cell. This habits could be useful due to the traditional targets of herpesviruses—neurons, which have a really uncommon cell construction.

A protracted method to the nucleus

Like different viruses, herpesviruses begin off by infecting cells which are uncovered to the atmosphere. However from there, they transfer on to nerve cells, the place they take up residency, persisting even when there is not any overt indications of an infection. These contaminated cells then function a launching level for re-establishing lively infections, inflicting lifetime issues for anybody unlucky sufficient to have been contaminated.

To determine this type of latent an infection, the herpesvirus has to take up residency in a cell’s nucleus. And that may be a good distance from the location of an infection, as nerve cells can ship out prolonged extensions referred to as axons that permit them to speak throughout totally different areas of the physique. The longest of those axons might be over a meter, so if the virus enters the neuron on the far finish of the axon, it must journey a good distance as a way to attain the nucleus.

In fact, the cell itself has to maneuver issues down these lengthy axons, so it has a system to handle that. Proteins type lengthy fibers that run the size of the axon; different proteins (referred to as motors) can latch on to those fibers and transit up or down the axon, hauling cargo as they go.

Herpesviruses have developed to make the most of this method. The virus encodes a protein that is included into its shell, and it has the flexibility to latch on to one of many motors. So as soon as it infects a nerve cell, it may be carried down the size of the axon prefer it was simply one other little bit of cargo. Because of this, the cell does a lot of the work wanted for the virus to take up residency.

A roadblock

Within the new examine, a bunch of US-based researchers was trying on the protein the virus makes use of to hitch a experience on the motor proteins. Earlier work had proven that the protein might latch on to 2 various kinds of motors (dynein and kinesin, for these of you up on this stuff), and the researchers have been occupied with seeing how the protein interacted with kinesin. So that they found out the place within the viral protein the interplay came about.

Turning to the viral gene that encodes this protein, they made mutations that eradicated its potential to seize on to kinesin. Viruses carrying these mutations have been not capable of unfold as soon as they contaminated a cell. This was a little bit of a shock, on condition that they need to nonetheless be capable of latch on to the second motor protein.

To get a greater sense of what was occurring, the researchers grew the virus in nerve cells that lacked kinesin. The virus readily moved down the axons, presumably on account of its interactions with the opposite motor. However as soon as it bought into the physique of the cell, the virus piled up close to the nucleus however wasn’t capable of enter it effectively.

However there is a huge distinction between the low effectivity seen on this experiment and the entire absence of an infection when the protein was mutated. The reason for this distinction: the virus really carries kinesin with it from the primary cell it infects.

ADVERTISEMENT

This was very onerous to detect, however the researchers ultimately found out a approach. They tagged kinesin with an enzyme that will trigger a chemical to alter coloration. They then confirmed that cells contaminated with the virus would additionally change coloration, indicating that the virus might carry the tagged kinesin into the cells.

The underside line

Placing this all collectively, it appears that evidently the virus hijacks the host’s transportation system in two methods. One among its personal proteins can latch on to a motor that carries the virus down a nerve system’s axon and will get it close to the nucleus. That very same protein additionally grabs a second motor and brings it into the cell with it. This motor permits the virus to make the transition from “close to the nucleus” to “inside it.”

Provided that nerve cells even have their very own kinesin, it is not clear why that is wanted—one thing the authors themselves acknowledge and are most likely engaged on. However the larger query is whether or not viruses carrying host proteins round is extra widespread than thought. Given how onerous it was to detect this course of at work within the herpesvirus, it is potential that it additionally occurs in different well-studied viruses, however we have simply missed it to this point.

Nature, 2021. DOI: 10.1038/s41586-021-04106-w  (About DOIs).