Bishop lab

Retroviral Replication Laboratory

: Areas of interest

Electron microscope image of mouse leukaemia virus-like particles containing a faulty p12 protein.

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Retroviruses cause severe diseases, including immunodeficiency and cancer. The human immunodeficiency virus (HIV) is the most widely known retrovirus due to its impact on human health. The latest figures (WHO/UNAIDS 2022) report that 39 million people globally are living with HIV/AIDS.

Innovative therapeutics for retroviral diseases will hopefully arise from a better understanding of how retroviruses reproduce in the cell, how they interact with host cell factors and how they subvert the host innate and adaptive immune systems.

The early stages of the retroviral life cycle are particularly attractive therapeutic targets, with several anti-retroviral drugs and cellular anti-viral factors inhibiting these steps.

However, numerous events that occur during these stages are still poorly understood. The three main projects in our laboratory aim to characterise the molecular events that occur once a retrovirus has entered a cell in order to fully understand retroviral replication and provide potential ways in which to manipulate these processes for the benefit of human health.

Early, post-entry stages of retroviral replication

Figure 1: Early, post-entry stages of retroviral replication

Figure 1: Early, post-entry stages of retroviral replication 

The retroviral life cycle is arbitrarily divided into two phases, early (from viral entry into a target cell up to integration) and late (from transcription of viral genes to release and maturation of viral particles).

The early post-entry stages begin once the viral core is released into the cell and end once the newly reverse transcribed viral cDNA is integrated into the host chromatin to form a provirus as indicated in steps 1-5.

Cellular factors that restrict replication (restriction factors) are shown in purple at the stage they inhibit. Lenacapavir (LEN, in yellow) is a drug that targets HIV-1 capsid and inhibits replication.