Severe lung damage is caused when flu is followed by infection with a measles-like virus, study finds

Infection with a measles-like virus causes catastrophic lung failure in ferrets previously infected with influenza virus or respiratory syncytial virus, according to a study led by researchers at the Georgia State University Translational Antiviral Research Center .

In the study published in Natural communications , researchers studied ferrets infected with a common respiratory virus such as respiratory syncytial virus or influenza virus, which causes flu-like illness in animals. A month after their full recovery, the animals were injected with a non-lethal strain of canine distemper virus (CDV), which is closely related to the human measles virus and which causes measles-like illness in ferrets. Two weeks later, the animals developed fatal hemorrhagic pneumonia.

“Acute lung failure after consecutive infection with two non-fatal respiratory viruses was unprecedented,” said study senior author Richard Plemper, Regents Professor at the Georgia State Institute for Biomedical Sciences and director from the Center for Translational Antiviral Research. “We found that these animals did not succumb to the viral infection, but to bacterial pneumonia because they became unable to prevent invasion of the lungs by commensal bacteria.”

By looking for differences in gene expression between animals infected or not with influenza virus, the study found that distemper infection results in the expression of a group of host-protective proteins in the lungs called trefoil factors.

“When the animals recovered from the flu, the clover factors were not upregulated, leaving them without protection against normally harmless bacteria,” said Robert Cox, assistant professor in the Center for Translational Antiviral Research and first author of the study. “Usually these animals recovered, but when exposed to CDV, this decrease in levels of protective host proteins led to the development of severe bacterial pneumonia.”

Using an experimental antiviral drug, GHP-88309, that Plemper developed in recent work, they were able to prevent fatal bacterial pneumonia even when treatment began very late after CDV infection.

“We do not currently know whether the measles virus causes worsening of disease following previous unrelated viral infections, but this adds greatly to the concerns about the resurgence of measles that we have seen in recent years around the world. ” said Plemper. “Measles is frequently followed by bacterial otitis media or bacterial pneumonia. A child’s history of viral illness may be an underestimated risk factor for developing these secondary sequelae.”

“In addition to discovering that previous infections may play a crucial role in disease severity, we were able to experimentally identify the window of opportunity to treat these viral infections and prevent the long-term immune suppression associated with measles-like illnesses “Cox said. .

The researchers demonstrated the benefits of treatment with GHP-88309 for more than seven days after the therapeutic vaccination window closed, “which introduces an additional new option to mitigate serious complications of measles-like illness,” said Cry.