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Naturally occurring lipid blocks RSV in lungs
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A naturally occurring lipid in the lung can prevent respiratory syncytial virus infection and inhibit spread of the virus after an infection is established, according to research published recently by researchers at National Jewish Health.
The findings, published in The Proceedings of the National Academy of Sciences, also help explain how the lipid, known as palmitoyl-oleoyl-phosphatidylglycerol, or POPG, helps the lung tolerate a daily barrage of inhaled inflammatory irritants.
“Our findings demonstrate that POPG is a potent antiviral agent both as a prophylactic and after infection has occurred,” Dennis Voelker, PhD, professor of medicine at National Jewish Health, said in a press release. “While these are still early studies, several characteristics of POPG make me believe that it has real potential as both an antiviral and anti-inflammatory treatment.”
POPG is one of several lipids in the fluid that lines the air sacs of the lungs.
Voelker and colleagues showed in cell-culture studies that inoculation with POPG before RSV exposure prevents RSV infection, as well as cell death and inflammation associated with RSV infection. In mice, prophylactic intranasal inoculation with POPG reduced the RSV infection-rate by a factor of 1,700 and prevented the infiltration of inflammatory cells into the lung that can cause tissue damage.
The researchers also showed that application of POPG to cells in culture after a viral infection is established arrests the spread of infection to neighboring uninfected cells.
“Our findings suggest that supplemental POPG may have significant potential for preventing RSV infections in vulnerable human populations, and treating infections after they become established,” wrote the authors in their paper.
The researchers demonstrate that POPG works by binding to RSV, thus preventing it from binding to receptors on cell surfaces.
Although molecules that look promising in cell-culture and mouse studies often fail to translate into therapeutic treatment in humans, Voelker and colleagues are optimistic about POPG’s chances for success, for a few reasons. For one, POPG occurs naturally in the lungs. The researchers have also administered massive doses to mice with no apparent ill effects. POPG also has been safely administered to millions of premature infants as part of a lipid mixture to protect their lungs. It is also a small molecule that is easily synthesized and is chemically stable.
The researchers next plan to evaluate POPG’s effectiveness against other pathogens, including influenza.
Numata M. PNAS. 2010; 107:320-325