Coxsackievirus B3 regulates T-cell infiltration into the heart by lymphocyte function-associated antigen-1 activation...

Area of Science:

• Virology
• Immunology
• Cardiology

Background:

• Coxsackievirus B3 (CVB3) infection is a known cause of myocarditis and dilated cardiomyopathy.
• CVB3-induced T-cell infiltration into cardiac tissue contributes to inflammation and cardiomyocyte injury.
• The precise molecular mechanisms driving T-cell infiltration in CVB3 infection are not fully understood.

Purpose of the Study:

• To elucidate the mechanism of T-cell infiltration during CVB3 infection.
• To identify the specific viral components responsible for T-cell activation and subsequent cardiac pathology.
• To explore potential therapeutic targets for CVB3-induced myocarditis.

Main Methods:

• Comparison of T-cell activation by wild-type (H3 WT) and attenuated (YYFF) CVB3 strains in vivo and in vitro.
• Assessment of T-cell activation through changes in lymphocyte function-associated antigen-1 (LFA-1) distribution.
• Investigation of the cAMP/Rap1 signaling pathway involvement in LFA-1 activation.
• Utilizing recombinant lentiviruses expressing CVB3 viral proteins (VP2) to determine their role in LFA-1 activation.

Main Results:

• CVB3 infection was confirmed to infect and activate T-cells, both in vivo and in vitro.
• Activated T-cells, identified by LFA-1 expression, were present in the hearts of CVB3-infected mice.
• LFA-1 activation on T-cells was mediated by the cAMP/Rap1 signaling pathway.
• Recombinant lentiviruses expressing CVB3 VP2 protein induced LFA-1 activation via increased cAMP, while the YYFF strain's VP2 did not.
• CVB3 infection elevates cAMP levels, activating Rap1 in T-cells, with VP2 being a critical factor.

Conclusions:

• CVB3 infection activates T-cells through a VP2-dependent mechanism involving the cAMP/Rap1-LFA-1 signaling axis.
• The viral protein VP2 plays a crucial role in mediating T-cell activation and infiltration during CVB3 infection.
• The identified VP2-cAMP-Rap1-LFA-1 pathway represents a promising therapeutic target for managing CVB3-induced myocarditis.