The work shows the web of interactions within cells as they try to ward off infections

UNTANGLING COMPLEX INTERACTIONS THAT GOVERN SICKNESS AND HEALTH, Professor Pinghui Feng studies viral infections and their interaction with cellular metabolic enzymes. These enzymes act on small molecules inside a cell to construct building blocks for cell growth and proliferation. But the way they worked in proteins wasn’t widely known — until now. 

Feng’s new study, published last month in the journal Nature Metabolism, is the result of the last nine years of study. His team focused on nicotinamide phosphoribosyltransferase (NAMPT), an enzyme that plays a key role in cellular health and metabolism. They found that the enzyme has two roles in adjusting how viruses can replicate in cells — and that the enzyme can also restrict viral infections by working on proteins in a similar way. “The virus actually needs the enzyme to make the metabolite and then to support the viral replication,” Feng said. “But on the other hand, if you lost it, you actually somehow increase viral replication. That’s what got us excited.” 

The research has implications for antiviral strategies and potential therapeutic applications, with ongoing efforts to develop small molecules targeting these enzymes for clinical use. It could prove important for people managing both viral infections and other types of health treatments, such as going through cancer treatment, Feng said. “If you are a cancer patient, and you receive inhibitors for the NAMPT, we’d predict that you may be more susceptible to herpes viruses or other types of viral infections,” he said. 

Feng was a professor at Keck School of Medicine of USC in 2017. He wanted to deepen his research into how metabolism is tied into immune response and moved to Ostrow in 2018. “I’m grateful for this support in the last seven or eight years,” Feng said. He added that during the past two years, he has had two grants, with two more coming in the next few years — all adding to the expanding knowledge of the metabolism and immune response system. His larger idea focuses on the molecular action of metabolic enzymes that regulate immune response, which has implications for a number of illnesses ranging from COVID to cancer. 

NAMPT is also very important in the brain, an area ripe for future studies. Neurotransmitters release and uptake via vesicles, Feng said, and he sees an analogy to the way that these viral particles get produced and released. Interestingly, one of the viral enzymes he’s studying inhibits NAMPT to promote viral infection and consequently accelerates neurodegeneration because NAMPT is necessary for normal physiology and function of the brain. 

He has also worked throughout the past decade to develop small molecules targeting several metabolic enzymes trying to treat viral infection and tumors by boosting the body’s immune response. “We want to really push these small molecules into the clinic,” he said. “That’s what I want to do during the next phase of my career.”