Proteomics reveals targets of HIV
An HIV protein called Vif destroys several key components of a key regulator in human cells, PP2A.
About 100 years since it was first transmitted to humans, the Human Immunodeficiency Virus (HIV) infects almost 40 million people worldwide and causes more than a million AIDS-related deaths every year. It is therefore critical to understand how HIV has been able to multiply and spread, and why infection with HIV causes AIDS. In the evolutionary “arms race” between viruses like HIV and the cells they infect, viruses try to enhance their ability to multiply, and cells try to resist. These interactions emphasise the processes that are most important for cells and viruses, and suggest new ways to treat HIV and other viral infections.
Proteomics is the large-scale study of molecules known as proteins, the critical building blocks of both cells and viruses. Edward Greenwood, Nicholas Matheson and colleagues use proteomics to measure how the abundance of proteins in human cells change during HIV infection, and identify new interactions between the virus and its host. The experiments distinguish more than 6,500 proteins, and reveal that an HIV protein called Vif destroys several key components of a cellular protein called PP2A. Previous studies have demonstrated that PP2A plays a critical role in regulating the activities of numerous other proteins and processes in cells. Greenwood, Matheson and colleagues further show that other HIV-related viruses that infect monkeys, apes and even sheep can also counteract PP2A, suggesting that this interaction has been important during host and virus evolution.
The next steps following on from this work are to find out why HIV attacks PP2A, and whether drugs that interfere with this interaction may help to treat HIV infection. A future challenge will be to investigate how HIV interacts with other cellular proteins highlighted by the proteomics approach.
To find out more
Read the eLife research paper on which this eLife digest is based: “Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants” (September 30, 2016).
