Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Vaccinia virus (a poxvirus) enters host cells via macropinocytosis, followed by endocytic internalization and membrane fusion.
• Different vaccinia virus strains exhibit distinct entry mechanisms, influencing host cell responses.

Purpose of the Study:

• To compare the host cell entry mechanisms of Western Reserve (WR) and International Health Department-J (IHD-J) vaccinia virus strains.
• To elucidate the signaling pathways, particularly Rho GTPases, involved in the distinct cellular responses induced by different viral strains.

Main Methods:

• Comparative analysis of viral entry pathways in HeLa cells.
• Investigation of Rho GTPase activation (Cdc42, Rac1) and downstream signaling.
• Use of inhibitors to probe tyrosine kinase, PI(3)K, and other kinase activities.
• Identification of ligands (phosphatidylserine) and receptors (EGFR) involved in macropinocytosis.

Main Results:

• WR strain MVs induce plasma membrane blebbing via Rac1 activation.
• IHD-J strain MVs induce filopodia formation via Cdc42 activation.
• Both strains utilize macropinocytosis triggered by virion-exposed phosphatidylserine and rely on EGFR, serine/threonine kinases, PKC, and PAK1.
• IHD-J strain entry is independent of genistein-sensitive tyrosine kinase and PI(3)K, unlike WR.

Conclusions:

• Distinct vaccinia virus strains employ different macropinocytic strategies for host cell entry.
• Viral strain variations lead to differential activation of Rho GTPases and signaling cascades.
• Understanding these strain-specific mechanisms is crucial for comprehending viral pathogenesis and host-pathogen interactions.