Coxsackievirus B3 entry into the host cell interferes with G-protein-mediated transmembrane signalling

Area of Science:

• Virology
• Cellular Biology
• Molecular Signaling

Background:

• Adenylyl cyclase (AC) is a key enzyme in transmembrane signaling pathways, regulating intracellular cyclic AMP (cAMP) levels.
• G-proteins are crucial mediators in signal transduction, linking cell surface receptors to intracellular effectors like AC.
• Viral infections can disrupt host cell machinery, including critical signaling pathways.

Purpose of the Study:

• To investigate the impact of Coxsackievirus B3 (CVB3) entry on the adenylyl cyclase transmembrane signaling system.
• To determine if CVB3 affects G-protein function and adenylyl cyclase activity in susceptible cell lines.

Main Methods:

• Utilized various cell lines (HeLa, HEp-2, Vero, green monkey kidney) for infection studies.
• Measured adenylyl cyclase activity in isolated plasma membranes after CVB3 preincubation.
• Assessed G-protein functionality by reconstituting AC activity in a cyc- mutant S49 cell line.
• Quantified intracellular cAMP levels in virus-infected cells.

Main Results:

• CVB3 infection significantly decreased adenylyl cyclase activity (10-20%) in multiple cell lines.
• G-protein ability to reconstitute AC activity was reduced in cells infected with CVB3.
• Intracellular cAMP levels markedly decreased (20-40%) in CVB3-affected cells.
• G-protein subunit content remained unchanged, indicating functional rather than quantitative alterations.

Conclusions:

• CVB3 entry disrupts the G-protein regulated adenylyl cyclase transmembrane signaling system.
• These functional alterations occur early, during the initial contact of CVB3 with the cellular plasma membrane.
• CVB3 infection leads to a significant reduction in cellular cAMP levels, impacting cellular homeostasis.