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B TrCP protein required for HIV to hide in host cells
Researchers are one step closer to understanding HIV
By Danielle Pycior | Bond LSC
Usually, the human immune system is good at recognizing infected cells and then killing them, but in the case of the human immunodeficiency virus (HIV), the virus has ways to hide. One of the ways is by using a viral protein called Vpu.
Vpu helps HIV survive by hiding the fact that it is infected from its host cells. For the past few years, researchers at the University of Missouri have helped uncover how this works.
“If you delete Vpu, those virus-infected cells are killed more efficiently,” said Marc Johnson, a Bond LSC scientist and professor in the Department of Molecular Microbiology and Immunology at the MU School of Medicine.
Understanding the Basics
Johnson and his lab study the connection between viruses and their hosts, trying to understand how viruses convince the host to allow them to keep replicating. In the case of HIV, Johnson and his colleagues discovered that Vpu only functions with the help of B TrCP, another protein.
“The virus doesn’t do anything by itself,” Johnson said. “It only has nine genes, while we have 30,000. It works by tricking its host genes to doing its bidding for it.”
Yul Eum Song, a graduate researcher in Johnson’s lab, explained that CRISPR technology allowed them to alter the genome to see how the proteins operate. CRISPR is a gene editing technique adapted from the DNA of bacteria that allows scientists to add, remove or edit specific locations in a genome.
“So, we use this to target and knock out genes to see if they’re necessary for the mechanism of HIV,” Song said.
They used CRISPR to remove the two types of B TrCP strands from the genome to see if Vpu would still hide HIV without its help.
“CRISPR has lots of applications, but the simplest, and the one I use is basically just molecular scissors that you can put into cells. It will make cuts in the genome wherever you want,” Johnson said.
By removing a certain gene, researchers can see how cells will react with and without certain proteins. In this case, Johnson and his team discovered that without either type of B TrCP strand expressed in the genome, Vpu couldn’t function, so it couldn’t avoid being killed by the immune system.
The magnitude of the HIV problem
“Thirty-five million people are infected with HIV. There are more people living with HIV today than ever in history, and the number keeps going up every year because once they’re infected, they’re infected for life,” Johnson said.
Johnson said that in terms of public health, HIV is a huge concern. Though treatments have gotten substantially better, they can have nasty side effects and don’t always work for everyone, sometimes resulting in death.
“By understanding the mechanisms of HIV, researchers can help combat the virus and create treatments,” Song said.
Both researchers pointed out how discoveries in the area of HIV can translate into other fields. The knowledge that virologists researching HIV find can help other scientists figure out what questions to ask and what functions to look for.
“We’ve learned about the cell and how our own cells work by studying the virus, but the virus is constantly utilizing and counteracting in ways that we’re still figuring out,” Johnson said.
Looking forward, Johnson and his lab are trying to find compounds that will block Vpu, and consequently allow the immune system to kill the HIV infected cells. Though the virus can never be completely removed from someone’s system, virologists search for treatments that can target and kill those cells that are expressing HIV.
“Part of the process is nailing down how VPU works, and a big part of what my lab is doing now is actually screening and testing compounds that do block VPU activity,” Johnson said. “That means if you have an infected virus, you treat them with this compound, and then they behave just like VPU was not there.”
By understanding how various proteins function in cells, researchers can get closer to understanding ways to combat viruses, and closer to understanding the micro-complexities that exist inside the human body.
This research was published in the Journal “Viruses” in Oct. 2018 and was funded by the National Institute of Allergy and Infectious Disease of the National Institutes of Health.