There is a
theory that non-cytolytic enterovirus has become resistant to interferon, due to the tiny deletions that have taken place in the RNA viral genome of non-cytolytic enterovirus (when enterovirus converts from its normal acute form into the chronic persistent non-cytolytic form, it does this by shedding off a tiny part of its RNA genome):
Basically, type I interferons destroy viral RNA inside a cell by sticking some Ifit1 proteins to this RNA. So interferon causes the production of Ifit1, and then Ifit1 then zaps the viral RNA in the cell.
Unfortunately the part that it sheds may be the very area that Ifit1 binds to.
In other words, Ifit1 is like a heat-seeking missile, and the target it homes in on is a specific part of the enterovirus genome. But that part of the genome has been removed, so the missile becomes useless.
So that may make non-cytolytic enterovirus RNA more invulnerable to the type I interferon immune response.
Interferon has other mechanisms of action, but this inactivation of viral RNA is an important one.
Whether type III interferon might have better luck in tackling non-cytolytic infection, I am not sure.
This paper indicates that both type I and type III interferons are strong inducers of Ifit proteins:
Other another mechanisms of action of interferon include inducing
RNase L, an enzyme which destroys all RNA with the cell, both viral and host (human) RNA.
In ME/CFS, famously this RNase L was
shown to have lower molecular weight than normal (small sized molecule), and initially it was thought this could impede its function, making it harder for RNase L to fight viral infections in the cell.
But if I remember correctly, I believe it was later shown that low molecular weight RNase L is actually more effective at destroying RNA.
Then there is an enzyme called
DICER which specifically targets viral dsRNA (viral double stranded RNA) in a cell. This viral dsRNA in the cell is generally more resistant to immune attack, so this makes DICER an interesting and useful antiviral enzyme.
It has been
found that type II interferon (interferon gamma) boosts DICER expression, but for some reason, type I interferons (like interferon alpha) suppress DICER expression.
Other factors which increase DICER are
mild hyperthermia, and intriguingly,
aerobic exercise. This may explain that while exercise can be very bad for ME/CFS (making patients crash, and making their ME/CFS worse), it's also possible that it does have these antiviral benefits. Refs:
here and
here.
DICER is inhibited by reactive oxygen species. Ref:
here
