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Essential Role of Clathrin and Lipid Rafts in pH-dependent Entry of Chandipura Virus: Independence From Caveolin
Ritudhwaj Tiwari1, Anurag Mishra2, Sheeba Rehman3
1Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, MP, India.
Insights
Chandipura virus (CHPV) enters host cells via a clathrin-dependent pathway that requires lipid rafts and acidic endosomes. Understanding these entry mechanisms is crucial for developing new antivirals against this neurotropic pathogen.
Area of Science:
- Virology
- Cell Biology
- Infectious Diseases
Background:
- Chandipura virus (CHPV) is an emerging neurotropic pathogen causing acute encephalitis in children, primarily in India.
- The mechanisms of CHPV host cell entry are not well understood, hindering the development of targeted therapies.
Purpose of the Study:
- To investigate the specific pathways utilized by CHPV for entry into host cells.
- To elucidate the role of cellular components like clathrin, lipid rafts, and endosomal pH in CHPV infection.
Main Methods:
- Utilized pharmacological inhibitors in Vero cells to block specific cellular pathways.
- Analyzed the impact of these inhibitors on CHPV entry and infection progression.
Main Results:
- CHPV entry was found to be dependent on clathrin-mediated endocytosis.
- The virus entry process requires intact lipid rafts but does not involve caveolin-mediated endocytosis.
- CHPV entry is pH-dependent, indicating the importance of endosomal acidification for viral uncoating.
Conclusions:
- CHPV utilizes a clathrin-dependent and pH-sensitive entry pathway.
- Lipid rafts play a critical role in CHPV cell entry.
- These findings provide insights for developing host-targeted antivirals against CHPV.
Abstract:
Chandipura virus (CHPV), a Rhabdoviridae family member, is an emerging neurotropic pathogen responsible for acute encephalitis outbreaks in children, mainly in India. Despite its public health relevance, the mechanisms underlying CHPV entry into host cells remain poorly understood. In this study, we used pharmacological inhibitors in Vero cells to dissect the virus's entry pathways. Our results show that CHPV entry is clathrin-dependent and requires intact lipid rafts but is independent of caveolin-mediated endocytosis. The process is pH-dependent, underscoring the role of endosomal acidification in viral uncoating. These findings on CHPV entry mechanisms offer valuable insights for developing host-targeted antivirals.
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