Studying lentiviruses to understand mechanisms, regulation and consequences of nucleic acid sensing

Activation of immune responses against viruses depends on detection in a process called sensing. We have discovered that cells briefly turn off sensing as they divide. We propose to discover how cell division regulates sensing, if this creates a window of susceptibility to infection and how viruses manipulate this to evade detection. Half of our DNA genome encodes viral sequences from ancient infections. We suspect that they play an important role in amplifying host defences because when viruses infect cells, we see these old sequences being switched on. We will determine how they are activated and whether they contribute to sensing infection. We will also determine the role of proteins called cyclophilins, which regulate sensing in interesting ways that we don't understand. Overall our work promises to reveal new ways that cells regulate sensing, how viruses escape them, and how we might manipulate sensing to treat infection and associated diseases.