Viral infections seem to disrupt the activity of a key cell-signaling pathway involved in muscle and skeleton health and healing, mental well-being, and prevention of obesity. The findings could help explain why we feel so down when dealing with a viral infection.
Image credits Jean-Louis Ractapopulous.
As if aches and coughs weren’t enough, being sick also makes you feel about as perky as a wet mop. Part of that is our own body’s fault — we’re drowsy so we’ll rest a lot, we get dehydrated to cough less and prevent pathogens from spreading, and so on. But researchers at UC Berkeley have found that it’s not a one-sided street — they report that viral infections dampen the activity in a key cell-signaling pathway called oxytocin receptor MAPK, or OXTR. This structure handles a wide range of processes, from promoting the development of trust and interpersonal bonding to underpinning muscle and bone maintenance and regeneration.
“Our results suggest that viral infections in general may play a role in decreasing muscle health and regeneration, a decline in metabolic health and a lower sense of well-being, as these rely on effective OXTR signaling,” said Irina Conboy, an associate professor in the Department of Bioengineering, whose lab performed the study.
Following the crumb trail
The team discovered this interaction by studying the standard vector used in gene therapy — viruses. Because most cells are really really small and pretty protective of their genes, scientists can’t poke around to rewrite their genomes. Viruses, however, are much simpler and have evolved specifically to paste new genes into cells’ DNA, so they’re the perfect tool when you need to put some new genes into a bacteria, for example. So they’re the go-to choice for most gene therapy applications.
As an experimental control measure — to ensure that the effects seen following therapy are caused by the spliced-in genes and not the viral infection itself — scientists test the effects of the viruses alone before having them deliver any genetic information. The viruses used in this step are called control viral vectors, and they aren’t supposed to change anything in a cell or organism, just interact with them.
The team showed however that even exposure to control vectors is enough to elicit noticeable differences in the subjects compared to healthy cells or animals by interfering with the strength of OXTR signaling. This reduced the regenerative ability of any direct descendants of these cells or tissues, in effect making them age more rapidly.
In one experiment mouse and human muscle cells that the team infected with control viral vectors showed a roughly 70% drop in OXTR strength. When testing to find out how an impaired OXTR pathway affects muscle cells, the researchers found that the vectors could decrease cell proliferation from 20% to a staggering 85%.
These findings suggest that there’s more happening that meets the eye when our bodies are fighting off pathogens, that there’s a kind of war of attrition going on — white blood cells have to fight the viruses off before the systems underpinning tissue maintenance are overwhelmed. Next on the list, the team says, is to work on developing a treatment to counteract this collateral damage caused by infections.
The full paper “Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin receptor and TGF-β/pSmad3” has been published in the journal Skeletal Muscle.
