Dengue and influenza coinfection in mice found to elevate risk of lung damage, death

February 23, 2017

Woman walking by public health billboard about pneumoniaLed by researchers from the UC Berkeley School of Public Health, a study recently published in the European Journal of Immunology examines the effects of influenza and dengue virus co-infection in mice. The study found that co-infection increases the disease severity, leads to severe lung damage, and increases the lethality of both viruses.

Cold and flu season is in full bloom across America. But in many regions of the world, including Brazil, Thailand, and Vietnam, flu season is also dengue season—a mosquito-borne virus responsible for 50-100 million infections every year. During the 2009 H1N1 influenza epidemic, countries such as Nicaragua, Puerto Rico, and India reported severe disease caused by a co-infection of dengue virus and influenza H1N1. 

Co-infections with influenza virus and bacteria are known to cause more serious complications in those infected, but little research has been done on the effects of co-infection between influenza and other acute viruses such as dengue.

“This was a particularly interesting study since it was inspired by the very large, atypical dengue epidemic in Nicaragua in 2009,” says Dr. Eva Harris, senior author and professor of Infectious Diseases and Vaccinology. “Our studies revealed that the only factor that could explain this epidemiological observation was the unusual overlap with the 2009 H1N1 influenza pandemic. We then decided to investigate the mechanism behind this increased disease severity by developing a mouse model of dengue and influenza virus co-infection.”

Study researchers infected mice with a strain of dengue virus within two days of administering a dose of H1N1. Although the doses were sublethal when administered alone, the combination produced a 90% lethality rate in the mice. They report that co-infection increases severity of disease, impairs host responses, and leads to severe lung damage.

In addition to elevated levels in the lungs, dengue virus displayed an increased presence in co-infected hosts’ livers and spleens. Because both viruses attack the lungs; however, pneumonia was the most common and devastating complication among the mice studied. 

The authors report that the mice involved were ill-equipped to fight both diseases simultaneously, dividing resources too thinly to be effective. “A ‘tug of war’ between the immune responses to infection with H1N1 or DENV resulted in only partial or intermediate responses that were not sufficient to fight co-infection with both viruses and may instead have caused severe immunopathology,” they explain.

The authors cite that the interaction between dengue and influenza evidenced by this research has already informed new treatment protocols in Nicaragua, and they recommend further guidelines for catching co-infection early, containing the spread of the disease, treating those already co-infected, and identifying populations most at risk who should be prioritized for vaccination. 

Authors of this study include Michael A. Schmid, Sanja Shah, and Eva Harris of UC Berkeley; Karla N. Gonzalez of UC Berkeley and Laboratorio Nacional de Virologıa, Centro Nacional de Diagnostico y Referencia, Ministerio de Salud, Managua, Nicaragua; Jose Pena of Lawrence Livermore National Laboratory; Matthias Mack of the Department of Internal Medicine, University Hospital Regensburg, Regensburg, Germany; and Laura B. Talarico of Fundacion INFANT, Buenos Aires, Argentina.

By Jaron Zanerhaft