The global HIV-1 pandemic is new only in the sense that it is the latest iteration in a conflict between humans and retroviruses that has spanned millions of years. Bearing witness to this, our genomes are littered with the DNA remnants of ancient retroviruses. These ‘human endogenous retroviruses’ (HERVs) are generally thought to be inert. In this thesis, I explore the hypothesis that HIV-1 has had to make a compromise in order to avoid extermination by a class of cellular defence factors that our cells evolved long ago in order to defend against ancient retroviruses. In disabling these defence factors to allow for its own replication, I posit, that HIV-1 enables the expression of the ancient retroviruses, as well as LINE-1 retroelements, in our genome. I propose to use this against the virus by targeted immune responses against HERV/LINE-1 antigens as a way of killing HIV-1-infected cells.

The global HIV-1 pandemic is new only in the sense that it is the latest iteration in a conflict between humans and retroviruses that has spanned millions of years. Bearing witness to this, our genomes are littered with the DNA remnants of ancient retroviruses. These ‘human endogenous retroviruses’ (HERVs) are generally thought to be inert. In this thesis, I explore the hypothesis that HIV-1 has had to make a compromise in order to avoid extermination by a class of cellular defence factors that our cells evolved long ago in order to defend against ancient retroviruses. In disabling these defence factors to allow for its own replication, I posit, that HIV-1 enables the expression of the ancient retroviruses, as well as LINE-1 retroelements, in our genome. I propose to use this against the virus by targeted immune responses against HERV/LINE-1 antigens as a way of killing HIV-1-infected cells.