Host Response and Pathogenesis of Respiratory Syncytial Virus Being Clarified Through Molecular Analyses

Techniques that determine the genetic activity of people with infections caused by respiratory syncytial virus (RSV) clarify host responses to the virus that are important in the establishment and persistence of infection. The genetic approach looks to have value when it comes to the diagnosis of RSV infections and further unraveling disease pathogenesis.

These advancements along with a further look ahead were the subject of talk given on Oct 27, 2016, by Octavio Ramilo, MD, Nationwide Children’s Hospital, Columbus, Ohio, at the annual meeting of the Infectious Diseases Society of America in New Orleans, Louisiana.

RSV infection is a prominent cause of bronchiolitis. A survey in the author’s hospital charted a steady increase in the prevalence of bronchiolitis from 59% of total cases in 2002 to 67% in 2007. This increase is reflected globally and is bad news for patients; RSV kills more children under the age of 1 (6.7% of global deaths) than any other pathogen, save malaria (11.8%).

The severity of RSV infection varies from a mild upper respiratory tract infection to a severe lower respiratory tract infection. “How do we explain the variability in clinical presentation? Likely it involves a complex interplay between the virus and the host,” said Dr. Ramilo in his talk.

Evidence from a number of studies has implicated viral load in disease severity. The host immune response was also posited to be involved. In the traditional scenario, RSV disrupts immune regulation, which normally functions to keep the activities of the adaptive and innate immune systems in balance, by inducing an exaggerated innate response. The consequence is lung inflammation and bronchiolitis.

However, evidence from studies conducted by Dr. Ramilo and others has turned the traditional view on its head. Instead, RSV infection appears to ratchet down innate immunity. In a study of 66 previously healthy children less than 2 years of age who had been hospitalized with a first episode of RSV bronchiolitis, nasal wash and blood samples were obtained within 24 hours of admission. Critically ill children with RSV admitted to the pediatric intensive care unit had significantly lower levels of innate cytokines compared with healthy controls and infants with less-severe RSV infection.

Transcriptional profile analysis has provided even greater clarity of immune response to RSV infection. RNA transcriptional profiling of 1883 febrile infants 60 days of age or younger was initiated by a cadre of researchers as part of the Pediatric Emergency Care Applied Research Network (PECARN) to explore the diagnostic utility of the approach. 163 (8.7%) of the infants had serious bacterial infections including bacteremia (2.0%), upper respiratory tract infection (7.4%), and bacterial meningitis (0.3%).

Transcriptional profiling revealed differences between the infants with bacterial and non-bacterial infections. The Molecular Distance to Health score developed by Dr. Ramilo and colleagues summarizes the transcription changes in RSV infection in a way that is clinically useful in gauging disease severity, length of hospitalization, and days of supplemental oxygen.

“RSV causes major morbidity and mortality worldwide. Host immune responses play a major role in disease severity. Transcriptomics is a promising tool to improve diagnosis and to study disease pathogenesis,” said Dr. Ramilo.

DISCLOSURES

• Advisory boards/consultant: AbbVie, Janssen
• Research grants: National Institutes of Health; NIAID and NICHD; Janssen

SOURCES

• Photos and tape of IDSA presentation
• Garcia CG et al. Pediatrics 2010: e11453-e1460
• Lozano R. et al. Lancet 2012. 380:2095-2128
• Garcia CG et al. Pediatric Infect Dis 2012. 31:86-89
• Mella C et al. 2013. J Infect Dis 207:564-573
• Mejias A et al. PLoS Medicine 2013. 10:e1001549

PIDS Caroline B. Hall Lectureship

• RSV Infection: Old Challenges and New Opportunities; Octavio Ramilo, MD, Nationwide Children’s Hospital, Columbus, Ohio

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.

Feature Picture Source: Yale Rosen / flickr / Creative Commons.