Noob biologist here. I suspect that at the first stage this means 'activating the virus by lysis of a surface/spike protein'? Seems kind of obvious, but I put it here in case 'proteolytic activation' is not in fact merely a subset of 'virus activation', and means something slightly different.

Second, if the above interpretation is correct, what precisely do we mean by virus activation? Is it the release of viral RNA into the host cell cytosol? This would be my guess, as it is necessary (sufficient?) for replication of viral RNA to commence, and viral replication to occur. Another idea is that 'virus entering host cell' is enough to constitute viral activation, though I suspect some viruses can enter cells and remain dormant there. Hardly seems like activation to me.

Would really appreciate clarification of this terminology so I don't have misconceptions when reading literature.

  • $\begingroup$ I don’t think “virus activation” means anything more than making a virus that is in an inactive state active. Why would you think otherwise and that it implies anything more specific? (And, unless you’ve performed some experimental procedure to remove organelles, it’s cytoplasm, not cytosol.) “Proteolytic activation” without any further qualification, only adds the mechanism (I assume you know what proteolysis is), so to find out its likely context I had to Google. You can too, but it’s sloppy writing. $\endgroup$
    – David
    Jul 14, 2020 at 19:57
  • $\begingroup$ @David but what is the defining difference between an active and inactive virus? What is the necessary process that makes an inactive virus now active? Is it the injection of rna into a host cell? Are the released replicated viruses then inactive until they start infecting other cells? Sorry if I'm being pedantic, but I really want to be clear on what is being referred to in the literature. $\endgroup$
    – Meep
    Jul 14, 2020 at 20:39
  • $\begingroup$ My point is there is no defining difference other than the English meaning of the word “inactive”. I hadn’t in general considered viruses having in inactive state, and there are so many different viruses that there can be no commonality. If someone writes “proteolytic cleavage of such and such a virus protein so that it is able to initiate membrane fusion” and thereafter abbreviated this as virus activation, that means something. Otherwise, not. As I wrote, sloppy writing — and incomprehensible too. The Emperor is naked. $\endgroup$
    – David
    Jul 14, 2020 at 20:50

1 Answer 1


Viruses all have some mechanism to enter cells' lipid membranes, and these need to be prevented from activating prematurely. Often this means the virus is in an inert state while it is assembled and trafficked out of the host cell, then activated by some chemical signal such as the low pH of inner endosomes. So "activation" is usually going to refer to a chemical change that removes the barriers to cell entry.

For example; in flaviviruses such as Zika or Dengue, the E glycoprotein that handles most of the host entry functions is assembled while bound to prM protein. Once virions are assembled with E in an inert arrangement, prM is proteolytically cleaved. When the new host cell absorbs the virion into an endosome and lowers the pH to digest it, the E glycoproteins rearrange into spikes that can penetrate the endosomal membrane and induce fusion with the viral membrane. If prM isn't cleaved, the virus can't infect cells. Here's a recent paper that discusses this process, with high resolution structures. For these viruses there are two rounds of activation, and only the first one is proteolytic.

  • $\begingroup$ For coronaviruses some cell's surface or endosome protease cuts some part of the viral surface protein (mainly S2' site but also pre-priming at S1/S2, the interaction of both is still unclear) which triggers the membrane fusion $\endgroup$
    – reuns
    Jul 15, 2020 at 12:00

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