Viral silencing and immune evasion pathways
Prof Paul Lehner
University of Cambridge
Invasion of our cells by foreign DNA threatens cellular integrity. Despite all organisms suppressing foreign DNA to protect their genome, DNA and RNA viruses have evolved to enter host cells and replicate while remaining undetected by the host’s immune system.
We want to understand how cells silence DNA and how viruses overcome this suppression. Our recent efforts to understand silencing of HIV-like viruses identified ‘HUSH’, a multi-component protein machine which creates a repressive environment that silences retroviruses. Retroviruses uniquely integrate their DNA into host genes, which explains why HIV is so difficult to eradicate. We will work out how HUSH silences viral DNA and how proteins from these retroviruses manipulate their host cells to avoid silencing and evade immune detection. We will use genetic and proteomic technologies to interrogate these host-virus interactions.
Our findings will help the development of new therapeutic tools to combat DNA and RNA viruses.