GRP78, a coreceptor for coxsackievirus A9, interacts with major histocompatibility complex class I molecules which...

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Viruses utilize specific cell surface molecules for attachment and entry, often involving multistep processes.
• Coxsackievirus A9 (CAV-9) infection requires integrin alpha(v)beta3 as a receptor and a 70-kDa protein (MAP-70) as a coreceptor.
• The precise roles of these molecules in CAV-9 entry remain to be fully elucidated.

Purpose of the Study:

• To investigate the attachment and entry pathway of Coxsackievirus A9 (CAV-9).
• To identify the 70-kDa major histocompatibility complex class I (MHC-I)-associated protein (MAP-70) involved in CAV-9 infection.
• To elucidate the functional association between GRP78, MHC-I, and CAV-9 entry.

Main Methods:

• Protein isolation and peptide sequencing to identify the 70-kDa protein.
• Fluorescence resonance energy transfer (FRET) to study molecular interactions.
• Assessing the requirement of GRP78 and MHC-I for CAV-9 infection and internalization.

Main Results:

• The 70-kDa protein was identified as GRP78, a heat shock protein 70 family member.
• GRP78 is expressed on the cell surface and associates with MHC-I molecules.
• CAV-9 infection necessitates GRP78 and MHC-I for efficient internalization into permissive cells.

Conclusions:

• GRP78 functions as a coreceptor for CAV-9, alongside integrin alpha(v)beta3 as the primary receptor.
• MHC-I molecules are essential for the internalization pathway of CAV-9 into mammalian cells.
• This study provides new insights into the CAV-9 life cycle, highlighting the roles of GRP78 and MHC-I in viral entry.