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

Monica E. Brint, Joshua M. Hughes, Aditya Shah, Chelsea R. Miller, Lisa G. Harrison, Elizabeth A. Meals, Jacqueline Blanch, Charlotte R. Thompson, Stephania Cormier, John Devincenzo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BackgroundLongitudinal 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.MethodsDuring 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 (AUC VL).ResultsThe 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 AUC VL. 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.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

Original languageEnglish (US)
Pages (from-to)872-880
Number of pages9
JournalPediatric Research
Volume82
Issue number5
DOIs
StatePublished - Nov 1 2017

Fingerprint

Respiratory Syncytial Viruses
Viral Load
Area Under Curve
Nose
Respiratory Syncytial Virus Infections
Mutation Rate
Virus Replication
Reverse Transcriptase Polymerase Chain Reaction
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants. / Brint, Monica E.; Hughes, Joshua M.; Shah, Aditya; Miller, Chelsea R.; Harrison, Lisa G.; Meals, Elizabeth A.; Blanch, Jacqueline; Thompson, Charlotte R.; Cormier, Stephania; Devincenzo, John.

In: Pediatric Research, Vol. 82, No. 5, 01.11.2017, p. 872-880.

Research output: Contribution to journalArticle

Brint, ME, Hughes, JM, Shah, A, Miller, CR, Harrison, LG, Meals, EA, Blanch, J, Thompson, CR, Cormier, S & Devincenzo, J 2017, 'Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants', Pediatric Research, vol. 82, no. 5, pp. 872-880. https://doi.org/10.1038/pr.2017.173
Brint, Monica E. ; Hughes, Joshua M. ; Shah, Aditya ; Miller, Chelsea R. ; Harrison, Lisa G. ; Meals, Elizabeth A. ; Blanch, Jacqueline ; Thompson, Charlotte R. ; Cormier, Stephania ; Devincenzo, John. / Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants. In: Pediatric Research. 2017 ; Vol. 82, No. 5. pp. 872-880.
@article{cba9518d227140bbacb91145eb5b34e1,
title = "Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants",
abstract = "BackgroundLongitudinal 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.MethodsDuring 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 (AUC VL).ResultsThe 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 AUC VL. 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.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.",
author = "Brint, {Monica E.} and Hughes, {Joshua M.} and Aditya Shah and Miller, {Chelsea R.} and Harrison, {Lisa G.} and Meals, {Elizabeth A.} and Jacqueline Blanch and Thompson, {Charlotte R.} and Stephania Cormier and John Devincenzo",
year = "2017",
month = "11",
day = "1",
doi = "10.1038/pr.2017.173",
language = "English (US)",
volume = "82",
pages = "872--880",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants

AU - Brint, Monica E.

AU - Hughes, Joshua M.

AU - Shah, Aditya

AU - Miller, Chelsea R.

AU - Harrison, Lisa G.

AU - Meals, Elizabeth A.

AU - Blanch, Jacqueline

AU - Thompson, Charlotte R.

AU - Cormier, Stephania

AU - Devincenzo, John

PY - 2017/11/1

Y1 - 2017/11/1

N2 - BackgroundLongitudinal 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.MethodsDuring 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 (AUC VL).ResultsThe 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 AUC VL. 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.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

AB - BackgroundLongitudinal 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.MethodsDuring 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 (AUC VL).ResultsThe 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 AUC VL. 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.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

UR - http://www.scopus.com/inward/record.url?scp=85031720410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031720410&partnerID=8YFLogxK

U2 - 10.1038/pr.2017.173

DO - 10.1038/pr.2017.173

M3 - Article

VL - 82

SP - 872

EP - 880

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 5

ER -