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Cyclophilin A Inhibits Human Respiratory Syncytial Virus (RSV) Replication by Binding to RSV-N through Its PPIase

Wenzhang Liang1,2,3, Yue Zhang1,2, Miao Li1,2

  • 1Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China.

Journal of Virology
|May 20, 2021
PubMed

Insights

Cyclophilin A (cypA) inhibits human respiratory syncytial virus (hRSV) replication by interacting with the viral N protein. This interaction, dependent on cypA

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human respiratory syncytial virus (hRSV) is a major cause of infant acute lower respiratory infection (ALRI).
  • Understanding virus-host interactions is crucial for developing effective antiviral strategies against hRSV.
  • Cyclophilin A (cypA) is a host protein whose role in hRSV infection requires further elucidation.

Purpose of the Study:

  • To investigate the role of cyclophilin A (cypA) in human respiratory syncytial virus (hRSV) replication.
  • To determine the mechanism by which cypA influences hRSV proliferation.
  • To identify specific viral components that interact with cypA during infection.

Main Methods:

  • Expression analysis of cypA in hRSV-infected patients, mice, and epithelial cells.
  • Functional assays using cypA knockdown and overexpression in host cells to assess viral replication.
  • Liquid chromatography-mass spectrometry (LC-MS) to identify cypA-interacting viral proteins.
  • Co-immunoprecipitation and immunofluorescence assays to confirm cypA-RSV N protein interaction.

Main Results:

  • hRSV infection significantly upregulated cypA expression in clinical samples, animal models, and cell cultures.
  • Reduced cypA levels enhanced hRSV replication, while increased cypA levels inhibited it.
  • cypA's inhibitory effect on hRSV replication was dependent on its peptidyl-prolyl cis-trans isomerase (PPIase) activity.
  • cypA was found to interact with multiple hRSV proteins, including RSV-N, RSV-P, and RSV-M2-1, with a specific interaction confirmed between cypA and RSV-N.

Conclusions:

  • Cyclophilin A (cypA) plays an inhibitory role in human respiratory syncytial virus (hRSV) replication.
  • cypA interacts with the viral nucleoprotein (RSV-N) via its PPIase activity, potentially impairing viral RNP complex formation and function.
  • These findings offer novel insights into cypA's antiviral mechanisms and suggest potential therapeutic targets for hRSV infection.

Keywords:
CSAPPIaseRSV-NcypAviral replication

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