Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants

Abstract

BACKGROUND Longitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans. METHODS During 2014–2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUCVL). RESULTS The 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUCVL. Six infants had detectable viral loads ≥ 1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P = 0.0259). All but one rebounder were <70 days old. CONCLUSION Infants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein

“…uals, who have a greater potential for resistance to develop due to higher viral loads and longer durations of viral shedding than those in immunocompetent adults (19,25). Characterization of the detected variants introduced synthetically into the RSV-F protein is the focus of ongoing studies.…”

Viral Load Dynamics and Clinical Disease Severity in Infants With Respiratory Syncytial Virus Infection

“…The variability in clinical presentations is likely the result of a complex interplay between viral factors and the host immune response [4][5][6][7][8][9]. A number of studies with variable designs have examined the association between viral loads (VL) and disease severity, with conflicting results.…”

Time-course of transcriptome response to respiratory syncytial virus infection in lung epithelium cells

“…The y-intercept of the regression line for RSV-A was of 5.27, suggesting that this viral load would be at the onset of symptoms (Day 0) (DeVincenzo, 2004). In a follow-up study of hospitalized RSV-infants younger than 1 year old, they also detected similar viral loads, approximately 6 log PFU/ml at the time of admission (Brint et al, 2017). This background indicates that the inoculum used in our study measured as log PFU/ml is comparable to in vivo situations, when we consider hospitalized infants, a risk group, whose dynamics of infection is important to understand.…”