The origins of HIV-1 through the lens of host-virus interactions

Michael Emerman (Fred Hutchinson Cancer Center, Seattle, US)

21 September 2023


Pratical info

12:00 - 13:00
Conference room Rosalind Franklin
research professional
Reduced mobility access

Humans encode seven APOBEC3 (A3) genes named A3A to A3H of which A3D, A3F, A3G, A3H are all capable of inhibiting  retroviruses by hypermutationLentiviruses such as HIV-1 have evolved to avoid the inhibition posed by A3 proteins by targeting them via a viral encoded Vif (Viral infectivity factor) protein. The A3 proteins have evolved under positive selection, and diversification of A3 allows host escape from Vif whereas adaptations in Vif enable cross-species transmission of primate lentiviruses. Resolution of the cryoEM structure of human A3G bound to HIV-1 Vif in complex with other host proteins highlights the Vif-A3G molecular arms race interface as well as a role for RNA as a molecular glue in this complex.  The Vif-A3G interactions inform the origins of HIV-1 through adaptations through primate hosts.

Michael Emerman is invited by Florence Margottin.

Michael Emerman is Professor at the Fred Hutchinson Cancer Center in Seattle. He has been a pioneer in several fields, from the distant discovery of the ability of HIV to infect cells outside mitosis, the discovery of the activity of specific viral proteins (the famous G2 arrest activity of Vpr), and then the extensive study of the "molecular arms race" between host factors and viruses along evolution (leading to the concept of paleovirology as a strategy to discover how ancient pathogens could shape our immune system today). To give a few more examples, his studies contributed to show how Trim5alpha, APOBEC3G and Tetherin/BST-2 proteins play a key role in the zoonotic transmission of lentiviruses, leading to HIV-1, and how SAMHD1 antagonism has changed in lentiviral evolution. More recently, he developed a technology for doing high throughput CRISPR/Cas screens for host factors that affect HIV replication and latency.