Dynamic Dystroglycan Complexes Mediate Cell Entry of Lassa Virus.

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Viral host range and disease potential are determined by receptor recognition.
• Lassa virus (LASV), a highly pathogenic emerging pathogen, utilizes dystroglycan (DG) as its primary receptor in human cells.
• DG interacts with various cellular proteins, forming tissue-specific complexes that may influence viral entry.

Purpose of the Study:

• To define the molecular composition of DG complexes in epithelial cells targeted by LASV.
• To investigate how the composition of DG complexes affects LASV entry.
• To understand the dynamics of DG complexes and their role in LASV-mediated endocytosis.

Main Methods:

• Unbiased shotgun proteomics to identify DG complex components.
• Biochemical approaches to analyze DG complex composition and function.
• Studies on endocytic pathways and signaling in LASV entry.

Main Results:

• The specific molecular composition of DG complexes in epithelial cells was characterized.
• DG complex composition was found to influence DG-mediated endocytosis and LASV entry.
• LASV entry via DG is faster than steady-state DG uptake and depends on receptor tyrosine kinases and p21-activated kinase signaling.

Conclusions:

• The molecular composition of DG complexes is a key determinant for productive LASV entry.
• LASV manipulates the DG-linked endocytic pathway for efficient entry.
• This interaction complexity offers potential cellular targets for antiviral interventions.