A new The Journal of Infectious Diseases study examines pathogenic or host genetic risk factors for RSV infection and whether certain viral variants are associated with long-term infection.
Study: Viral genetic determinants of long-term respiratory syncytial virus infection in infants in a healthy term birth cohort. Image credit: ART_ur / Shutterstock.com
The 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 have been infected with RSV at least once. RSV primarily infects the epithelium of the lower and upper respiratory tract; however, it has also been found in non-respiratory sources. While RSV typically causes an acute respiratory infection, it can also lead to persistent or long-term illness in some individuals.
The prolonged shedding of RSV in infants after initial infection has been observed to prolong the mean duration of viral shedding. However, it is not known whether specific viral factors lead to long-term infection in infants.
It is essential to understand the features of prolonged infection as it can increase the rate of transmission and cause developmental changes in the airway epithelium of young patients. The reservoir for RSV is also not understood, with some strains of RSV believed to remain in circulation at low levels in the community, while others may remain seasonal.
About the study
The current study involved healthy term infants suffering from long-term RSV infection. A viral genome-wide association study (GWAS) using RSV whole genome sequencing has been conducted to understand the relationship between long-term RSV infection in infants and viral genotypes.
Human GWAS was performed to analyze the impact of first-year RSV infection risk on genotype. In addition, the local immune response to RSV was assessed along with an analysis of all viral sequence data.
Finally, a summary was made with all functional data of the identified variant.
A total of 19 infants met the criteria for long-term infection, defined as acute respiratory infection with two or more RSV polymerase chain reaction (PCR) positive nasal samples 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 the genotypes of the infants. In addition, long-term infection was caused by viruses of different phylogenetic clades compared to a single specific clade. Similar RSV sequences were observed for initial and subsequent viral detection, suggesting that these were long-standing infections.
A genetic association was observed between long-term infection and the leading variant, and no other variants were found to correlate with the leading variant. The genotypes p.E123K/D and p.P218T/S/L were mainly associated with long-term infection; however, there was insufficient information on the effects of the two variants on regional or local RSV G protein structure. In addition, the impact on glycosylation was undetermined.
The current study identified RSV variants that led to long-term infection in otherwise healthy infants; however, no information was obtained on the host’s genetic susceptibility to RSV infection.
Understanding viral and host mechanisms that result in long-term infection may be helpful in determining strategies that can manage both the short- and long-term effects of RSV infection. In addition, identifying RSV variants that cause long-term infection may also help improve vaccine design.
Further research is needed to determine the reservoir for RSV and its capacity for long-term infection in immunocompetent hosts.
The current study was not designed to examine duration of infection and required additional sampling. In addition to a small cohort size, the researchers were only able to analyze the host’s genetic risk for infection, rather than long-term infection. Finally, the modulating effects of maternal antibody levels on the infants were not measured.
- Lawless, D., McKennan, CG, Das, S.R., et al. (2022). Viral genetic determinants of long-term respiratory syncytial virus infection in infants in a healthy term birth cohort. The Journal of Infectious Diseases. doi:10.1093/infdis/jiac442.