Curing infected cells instead of killing them

Once a cell is infected, our immune system clears the infection not by targeting the virus, but by simply killing the infected cell.  Antibodies are also an important part of our defense against viral infections, but their function is limited to targeting viruses floating around outside the cell.  It is believed the once the virus enters the cell, it’s safe from antibodies.  But a recent study suggests that this may not be true; it seems that antibodies can eliminate viruses from inside cells too.  This is particularly groundbreaking because this may be a mechanism to cure infected cells, rather than just killing them.

Researchers identified a protein called TRIM21 that binds antibodies, but it was localized to the cell’s cytoplasm.  Why would it be there, when antibodies are secreted?  It seems that sometimes viruses can enter a cell with antibodies bound to it.  While some antibodies are neutralizing, meaning that they prevent attachment to the receptor, others are not.  If the virus is coated with these non-neutralizing antibodies, it can still enter, and it bring the antibodies in with it.  TRIM21 recognizes these internalized antibodies, with virions attached to them, and then targets it for destruction in a cellular blender called the proteasome. In an appropriately named “fate of capsid” experiment, the researchers showed that antibody bound adenovirus capsid proteins were being degraded as soon as 2 hours after infection and that the degradation required both the proteasome and TRIM21.  So the virus is being destroyed quickly, before it gets the chance to replicate.

As always, this study introduces many new questions.  They used adenovirus, which causes mild respiratory infections, but does the mechanism extend to other non-enveloped viruses? Can this mechanism be used to improve existing vaccines or develop new ones? How important is this mechanism in the overall response to viral infection?  Have viruses evolved mechanisms to block TRIM21?