1719. Transcriptome analyses of human macrophages infected with clinical isolates of respiratory syncytial virus reveal distinct patterns of innate immune activation
Session: Poster Abstract Session: Studies of the Interface of Host-Microbial Interaction
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • ISDA_Poster_2013.10.pdf (1.0 MB)
  • Background: The mechanisms of pathogenesis of respiratory syncytial virus (RSV) remain poorly defined. It is not clear why certain infants are prone to severe RSV infection. We sought to determine whether there was variation in the innate immune response to RSV among individuals. Likewise, we sought to determine whether clinical isolates of RSV differ in their capacity to activate gene expression during infection of primary human macrophages. 

    Methods: Clinical isolates of RSV were used to infect primary human macrophages from a variety of donors. Concentrations of secreted cytokines were determined by Bio-Plex assay. The transcriptome of infected cells were determined utilizing RNA-SEQ technology. Heatmaps of gene expression dynamics in infected cells were generated with the Spotfire Decision Site 9 software. Gene subsets were created from the list of genes involved in response to viral infection. Functional analysis of identified genes was performed with Ingenuity Pathway Analysis.

    Results: RSV activated genes involved in multiple processes including response to virus entry, virus replication, virus recognition, activation of the innate immune system and response to interferon. Overall, at least 2 distinct patterns were observed among donors suggesting that the innate response to viral infection differs among individuals. Furthermore, we observed distinct patterns of activation of genes among different clinical isolates of RSV. These data suggest that there is significant variability of clinical isolates of RSV to activate or inhibit the innate immune system. Signaling pathway analyses revealed that the magnitude of pathway activation, rather than the specific pathways activated accounted for the differences in gene expression among the viruses studied. 

    Conclusion: These data suggest that the innate immune response to RSV may determine the severity of disease. Our data also indicates that RSV strains are not homogeneous with regard to activation or inhibition of the innate immune response in primary human macrophages. Identification of the viral genetic polymorphisms associated with activation or inhibition of the innate immune response may lead to the development of effective antiviral agents and vaccines.

    Ruth Levitz, PhD1, Igor Dozmorov, PhD2, Ran Song, PhD2, Edward K. Wakeland, PhD2 and Jeffrey S. Kahn, MD, PhD1,3, (1)Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, (2)Immunology, University of Texas Southwestern Medical Center, Dallas, TX, (3)Microbiology, University of Texas Southwestern Medical Center, Dallas, TX

    Disclosures:

    R. Levitz, None

    I. Dozmorov, None

    R. Song, None

    E. K. Wakeland, None

    J. S. Kahn, None

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