Assembly Cofactors of HIV-1

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Lay summaryHIV-1 is the virus responsible for the worldwide AIDS pandemic. Although progression to AIDS in the majority of HIV-infected patients can be prevented with antiretroviral drugs, allowing people infected with HIV to life a normal life, there is no cure and such drugs must be taken for the rest of the patient's life. Additionally, HIV sometimes develops resistance to commonly used antiretrovirals and the drugs themselves can cause serious co-morbidities, making management of the condition more difficult. Further scientific research into the fundamental biological principles of HIV replication and infection will facilitate the development of new classes of drug, giving clinicians more options to manage HIV. Increasing our basic understanding of the virus lifecycle will also help work that aspires to develop life time cures for HIV infection.In its replication cycle, HIV infects a cell and inserts a DNA copy of its RNA viral genome into the cellular genome. The cellular molecular machinery is then co-opted to produce all the viral proteins that are needed to form new infectious virus particles. These proteins plus the virus genome then move to the cell membrane where they assemble into new virus particles and bud away from the cell surface; these particles proceed to infect new cells thereby sustaining and spreading the infection. There are several lines of scientific evidence indicating that the process of HIV-1 assembly is dependent on interactions between virus components and various cellular cofactors. However, current knowledge of the identities of these critical cellular cofactors is far from complete. This provides us with an important opportunity to discover novel regulators of HIV replication, whose therapeutic inhibition has the potential to block virus growth.Our proposed research will: i) use state-of-the-art technologies to identify novel cofactors of HIV assembly, and ii) define the molecular mechanisms that underlie their interactions with virus components and determine how these promote assembly of the virus. As these cofactors are important for the virus to replicate, their identification will provide the evidence-based platform from which to explore the development of new antiretroviral drugs.