1302. Induction of Inflammatory Cytokines by Clinical Isolates of Respiratory Syncytial Virus is Strain Specific
Session: Poster Abstract Session: Viral Immunology and Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in pathogenesis and virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines.

Methods: We screened a bank of genetically diverse clinical isolates of RSV for their ability to induce inflammatory cytokines in cell culture. These clinical isolates were obtained from a clinical microbiology laboratory over a period of many years. Plaque-purified viruses were used to infected human pulmonary epithelial A549 cells and secreted IL-1α, TNFα and IL-6 were measured by ELISA or Bio-Plex assay. 

Results: Several subgroup B isolates were identified that differed in their ability to induce IL-1α, TNFα and IL-6. RSV strains NH1067 and NH1125 were chosen for further evaluation. Sucrose-purified virus was used to infect A549 cells (moi of 1) and IL-6 concentrations in cell culture supernatant were measured at multiple time points post-infection. Overall, the level of induction of IL-6 by NH1125 was statistically significantly greater than NH1067. The induction of IL-6 was dependent on viral transcription and/or replication as infection with UV-inactivated virus did not induce IL-6.  The difference in IL-6 induction could not be explained by differences in viral replication kinetics as the intracellular level of RSV RNA, as determined by real time, RT-PCR, was indistinguishable between the 2 strains. Full genome sequencing of the 2 strains revealed >180 polymorphisms and 4 deletions; 2 in non-coding regions and 2 in the RSV G gene. Of the polymorphisms, 141 occurred in coding regions and ~30 resulted in amino acid changes in 7 of the RSV genes.  

Conclusion: These data suggest that RSV strains may not be homogeneous with regard to pathogenesis or virulence. Identification of the genetic polymorphisms associated with cytokine induction may lead to the development of effective antiviral agents and vaccines.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Ruth Levitz, PhD1, Rachel Wattier, MD2, Alexandra Solomon1, Isaac Lazar3 and Jeffrey Kahn, MD, PhD1, (1)Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, (2)Yale Unviersity School of Medicine, New Haven, CT, (3)Pediatrics, Yale Unviersity School of Medicine, New Haven, CT

Disclosures:

R. Levitz, None

R. Wattier, None

A. Solomon, None

I. Lazar, None

J. Kahn, None

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