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Measuring Influenza Neutralizing Antibody Responses to A(H3N2) Viruses in Human Sera by Microneutralization Assays Using MDCK-SIAT1 Cells
Published on: November 22, 2017
Human parainfluenza virus 3 neuraminidase activity contributes to dendritic cell maturation
Maria-Arantxa Horga1, Salvador Macip, Ana C Tuyama
1Department of Pediatric Infectious Diseases, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1657, New York, NY 10029, USA. maria.horga@mssm.edu
Abstract:
Mechanisms of dendritic cells (DCs) immunomodulation by parainfluenza viruses have not been characterized. We analyzed whether the human parainfluenza 3 (HPF3) virus hemagglutinin-neuraminidase glycoprotein (HN) might influence DC maturation. HN possesses a receptor binding function and a neuraminidase or desialidating activity. To assess whether the neuraminidase activity of HN affects DC maturation, human myeloid DCs were exposed to either live or UV-inactivated HPF3 viruses containing wild type or a mutated form of HN with decreased neuraminidase activity. Exposure of human DCs to either UV-inactivated or live virus induced up-regulation of CD83 and CD86 surface markers, morphological changes, and a cytokine expression pattern consistent with maturation. However, the level of maturation was found to be lower in DCs infected with the neuraminidase deficient variant as compared to the wild type. These results suggest that during the course of viral infection, HN's neuraminidase activity may play an important role contributing to maturation and activation of DCs.
Insights
Human parainfluenza 3 virus hemagglutinin-neuraminidase (HN) activity influences dendritic cell (DC) maturation. HN
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Mechanisms of dendritic cell (DC) immunomodulation by parainfluenza viruses remain largely uncharacterized.
- The hemagglutinin-neuraminidase (HN) glycoprotein of human parainfluenza 3 (HPF3) virus possesses receptor binding and desialylation functions.
- Investigating HN's role in DC maturation is crucial for understanding viral pathogenesis and immune responses.
Purpose of the Study:
- To determine if the hemagglutinin-neuraminidase (HN) glycoprotein of human parainfluenza 3 (HPF3) virus influences dendritic cell (DC) maturation.
- To elucidate the specific contribution of HN's neuraminidase activity to DC activation and maturation.
- To analyze the impact of wild-type versus neuraminidase-deficient HN on DC surface marker expression and cytokine profiles.
Main Methods:
- Human myeloid dendritic cells (DCs) were exposed to live or UV-inactivated HPF3 viruses.
- Viruses utilized either wild-type HN or a mutated form with reduced neuraminidase activity.
- DC maturation was assessed by analyzing surface marker upregulation (CD83, CD86), morphological changes, and cytokine expression patterns.
Main Results:
- Exposure to both live and inactivated HPF3 viruses induced DC maturation, evidenced by CD83 and CD86 upregulation and altered cytokine profiles.
- DCs infected with the neuraminidase-deficient HN variant exhibited a lower level of maturation compared to those infected with wild-type HN.
- These findings indicate that HN's neuraminidase activity plays a significant role in promoting DC maturation.
Conclusions:
- The neuraminidase activity of the HPF3 virus HN glycoprotein is a key factor in modulating dendritic cell (DC) maturation.
- HN's desialylation function contributes to the activation and maturation of DCs during parainfluenza virus infection.
- Understanding this mechanism provides insights into host-pathogen interactions and potential therapeutic targets.
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