Vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture

Schmidt FI, Bleck CK, Helenius A, Mercer J (2011) EMBO J 30 (17): 3647-3661

Speaker: Hsin-Pei Hsieh (謝欣倍)                                Time: 13:00~14:00, Dec. 28, 2011

Commentator: Dr. Shun-Hua Chen (陳舜華老師)       Place: Room 601

Abstract:

Vaccinia virus (VACV) belongs to the poxvirus family. It produces two different types of virions - mature virions (MVs) and extracellular virions (EVs). Viral membrane fusion with the cellular membrane plays an important role in the replication process. Following fusion, the viral genome is released into the cytosol then start to replication. MVs are released after lysis of infected cells and mediate cell-to-cell transmission. EVs exit the cell by exocytosis and are required for spreading of the virus, but the mechanism of how EVs are internalized is unclear. EV particles cover MV-like particles with extra outer membrane. Therefore, it is hypothesized that EVs and MVs infect the host cell by different mechanism. The outer membrane of EV particles contain specific proteins and it is fragile and sensitive to reduced pH in vitro¹_. In this study, EV particles trigger both fluid-phase uptake and extensive blebbing which are similar to that observed during infection with MV particles. The requirement for PAK1, PKC, smMLCK activity, actin rearrangement, and sodium-proton exchangers indicated that EV particles infect the host cell by macropincytosis². The outer membranes of EV particles are destroyed at low pH. The authors suggest that intact EV particles require an environment with low pH to break the outer membrane so that MV-like particles can be released into cytoplasm. In conclusion, this study demonstrated that EV particles internalized bymacropinocytosis, and acidification of endocytic compartments is required for the successful entry of EVs

References:

1.          Law M, Carter GC, Roberts KL, Hollinshead M, Smith GL (2006) Ligand-induced and nonfusogenic dissolution of a viral membrane. Proc Natl Acad Sci USA 103: 5989–5994

2.          Mercer J, Helenius A (2009) Virus entry by macropinocytosis. Nat Cell Biol 11: 510–520