Study: Viral genetic determinants of prolonged respiratory syncytial virus infection among infants in a healthy term birth cohort. Image Credit: ART_ur / Shutterstock.com

Researchers identify new RSV variant associated with prolonged infection

A new The Journal of Infectious Diseases The study examines pathogen or host genetic risk factors for RSV infection and whether certain viral variants are associated with prolonged infection.

Study: Viral genetic determinants of prolonged respiratory syncytial virus infection in infants from a healthy term birth cohort. Image Credit: ART_ur / Shutterstock.com

Transmission of RSV

Human orthopneumovirus, more commonly known as respiratory syncytial virus (RSV), can cause significant mortality and morbidity worldwide.

All children between the ages of two and three are infected with RSV at least once. RSV mainly infects the epithelium of the lower and upper respiratory tract; however, it has also been found in sources other than the respiratory tract. Although RSV usually causes an acute respiratory infection, it can also cause persistent or prolonged illness in some people.

Prolonged RSV shedding in infants after first infection has been observed to increase the average duration of viral shedding. However, it is not known whether specific viral factors lead to prolonged infection in infants.

Understanding the characteristics of prolonged infection is critical because it can increase transmission rates and cause changes in the development of the airway epithelium in young patients. The RSV reservoir is also not understood, with some strains of RSV remaining circulating at low levels in the community, while others may remain seasonal.

About the study

The current study involved healthy full-term infants with prolonged RSV infection. A viral genome-wide association study (GWAS) was performed using RSV whole genome sequencing to understand the relationship between prolonged RSV infection in infants and viral genotypes.

The human GWAS was performed to analyze the impact of the risk of RSV infection in the first year on the genotype. Additionally, the local immunological response to RSV was assessed, along with an analysis of all viral sequence data.

Finally, a summary including all the functional data of the identified variant has been provided.

Study results

A total of 19 infants met the criteria for prolonged infection, defined as acute respiratory infection with at least two RSV polymerase chain reaction (PCR) positive nasal specimens with more than 15 days between the two test dates.

The mean RSV Ct value of the first infection was 25.9, while the second was 31.6. The average number of days between the two infections was 29 days.

RSV infection had little or no impact on infant genotypes. Moreover, prolonged infection was caused by viruses from different phylogenetic clades compared to a single specific clade. Similar RSV sequences were observed for both initial and subsequent virus detection, suggesting that these were prolonged infections.

A genetic association between prolonged infection and the main variant was observed, with no other variant correlating with the main variant. The p.E123K/D and p.P218T/S/L variant genotypes were mainly associated with prolonged infection; however, information on the effects of the two variants on regional or local RSV G protein structure was insufficient. Additionally, the impact on glycosylation was undetermined.

conclusion

The current study identified RSV variants that led to prolonged infection in otherwise healthy infants; however, no information on the host’s genetic susceptibility to RSV infection has been obtained.

Understanding the viral and host mechanisms resulting in prolonged infection can be helpful in determining strategies that can control the short- and long-term impacts of RSV infection. Additionally, identifying RSV variants causing prolonged infection may also help improve vaccine design.

Further research is needed to determine the reservoir of RSV, as well as its ability to sustain infection in immunocompetent hosts.

Limits

The current study was not designed to examine the duration of infection and required additional sampling. In addition to a small cohort size, the researchers were only able to analyze the genetic risk of host infection rather than prolonged infection. Finally, the modulating effects of maternal antibody levels on infants have not been measured.

Journal reference:

  • Lawless, D., McKennan, CG, Das, SR, et al. (2022). Viral genetic determinants of prolonged respiratory syncytial virus infection in infants from a healthy term birth cohort. The Journal of Infectious Diseases. doi:10.1093/infdis/jiac442.

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