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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Association of disease severity and genetic variation during primary Respiratory Syncytial Virus infections
William Bender1, Yun Zhang2, Anthony Corbett3
1Division of Infectious Disease, Department of Medicine, School of Medicine and Dentistry, University of Rochester, University of Rochester Medical Center, Rochester, NY, USA.
Insights
Respiratory Syncytial Virus (RSV) genetic variations, specifically in the G and M2-2 genes, are linked to disease severity in infants. Phylogenetic lineage also plays a role in how severe RSV infection becomes.
Area of Science:
- Virology
- Pediatric Infectious Diseases
- Genetics
Background:
- Respiratory Syncytial Virus (RSV) causes a spectrum of illness in young children, from mild to life-threatening.
- Previous studies suggest a link between RSV subtypes/lineages and disease severity, but findings are inconsistent.
- The association between specific RSV gene variations and disease severity remains largely unexamined.
Purpose of the Study:
- To investigate the association between RSV genetic variability and disease severity in infants.
- To explore the role of phylogenetic lineage and specific gene mutations in RSV disease outcomes.
Main Methods:
- Analysis of whole-genome RSV sequences from nasal swabs of infants with mild or severe RSV disease.
- Utilized overlapping PCR and next-generation sequencing for genetic analysis.
- Employed both phylogenetic and non-phylogenetic statistical methods to correlate RSV genotype with disease severity.
Main Results:
- RSV subtype B (RSVB) was statistically associated with increased disease severity.
- Phylogenetic clustering of traits correlated significantly with disease severity.
- GA1 clade RSV was linked to severe disease, while GB1 clade was associated with mild disease.
- Variations in the G and M2-2 genes were significantly associated with disease severity, with specific residues identified.
Conclusions:
- Phylogenetic lineage and genetic variability within RSV's G and M2-2 genes may influence disease severity in infants during their first RSV infection.
- These findings highlight potential genetic markers for predicting RSV disease severity.
Background:
Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored.
Methods:
Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity.
Results:
The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity.
Conclusion:
These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.
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