Abstract

Neutralizing antibodies reduce infection by interfering with viral entry. However, non-neutralizing antibodies (nnAbs) also provide immunity against diverse viruses including retroviruses, arenaviruses, influenza viruses and rotaviruses. The mechanism by which many of these nnAbs provide protection has been a longstanding mystery. Our work shows that nnAbs can inhibit infection by engaging the cytosolic antibody receptor TRIM21 to result in a range of different outcomes.

For enveloped viruses, we have demonstrated that nnAbs can recruit TRIM21 to promote the induction of cytotoxic T cells. This highlights that cooperativity between both arms of adaptive immunity is crucial for successful resolution of viral infection, and raises the possibility of new vaccine approaches.

For viruses with multiple capsid layers such as rotavirus, intracellular antibodies engage TRIM21 to target virus particles to the proteasome. We have shown that manipulation this pathway affects susceptibility to infection in a mouse rotavirus model, and propose that measuring these antibodies will predict vaccine efficacy.