Host cell factors in filovirus entry: novel players, new insights

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Filoviruses cause severe hemorrhagic fever with high mortality.
• Cellular factors enabling filovirus spread are potential therapeutic targets but not fully understood.
• The filovirus glycoprotein (GP) is crucial for viral entry into host cells.

Purpose of the Study:

• To review recent advances in understanding the molecular interactions governing filovirus entry.
• To discuss the implications of these interactions for filovirus cell tropism.

Main Methods:

• Review of recent studies on host cell molecules engaged by filovirus GP.
• Analysis of findings related to lectin binding, tyrosine kinase receptors, TIM-1 interactions, and Niemann-Pick C1.
• Examination of mutagenic and structural analyses defining GP interaction domains.

Main Results:

• Filovirus GP binds to cellular lectins, concentrating virions on susceptible cells, particularly macrophages and dendritic cells.
• Tyrosine kinase receptors facilitate macropinocytic uptake independently of GP binding.
• GP interaction with human T cell Ig mucin 1 (TIM-1) may facilitate mucosal epithelial cell infection.
• Niemann-Pick C1 is essential for GP-mediated viral envelope fusion with host cell membranes.
• Specific GP domains interacting with host factors have been identified.

Conclusions:

• Elucidation of molecular interactions provides critical insights into filovirus cell entry mechanisms.
• Understanding these host-pathogen interactions is vital for developing targeted interventions against filoviruses.
• This knowledge advances our comprehension of filovirus cell tropism and pathogenesis.