Coxsackievirus infection induces autophagy-like vesicles and megaphagosomes in pancreatic acinar cells in vivo.
Autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. Tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. Herein, we report on in vivo studies that evaluate the effects on autophagy of coxsackievirus B3 (CVB3). We show that in pancreatic acinar cells, CVB3 induces the formation of abundant small autophagy-like vesicles and permits amphisome formation. However, the virus markedly, albeit incompletely, limits the fusion of autophagosomes (and/or amphisomes) with lysosomes, and, perhaps as a result, very large autophagy-related structures are formed within infected cells; we term these structures megaphagosomes. Ultrastructural analyses confirmed that double-membraned autophagy-like vesicles were present in infected pancreatic tissue and that the megaphagosomes were related to the autophagy pathway; they also revealed a highly organized lattice, the individual components of which are of a size consistent with CVB RNA polymerase; we suggest that this may represent a coxsackievirus replication complex. Thus, these in vivo studies demonstrate that CVB3 infection dramatically modifies autophagy in infected pancreatic acinar cells.
Kemball
Christopher C
CC
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Alirezaei
Mehrdad
M
Flynn
Claudia T
CT
Wood
Malcolm R
MR
Harkins
Stephanie
S
Kiosses
William B
WB
Whitton
J Lindsay
JL
D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D003384:Coxsackievirus Infections / Q000503:physiopathology*; D029822:Enterovirus B, Human; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D010179:Pancreas / Q000166:cytology* / Q000821:virology; D010588:Phagosomes / Q000648:ultrastructure / Q000821:virology*
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins