Keratins provide virus-dependent protection or predisposition to injury in coxsackievirus-induced pancreatitis

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: DM Toivola, SE Ostrowski, H Baribault, TM Magin, AI Ramsingh, MB Omary
Publiceringsår: 2009
Tidskrift: Cell Health and Cytoskeleton
Volym: 1
Artikelns första sida, sidnummer: 51
Artikelns sista sida, sidnummer: 65


Abstrakt

Keratins 8 and 18 (K8/K18) are the two major intermediate filament
proteins in hepatocytes and pancreatic acinar cells. Acinar cell
keratins are organized as cytoplasmic and apicolateral filaments. An
important role of hepatocyte K8/K18 is to maintain cellular integrity,
while this cytoprotective function of K8/K18 is not evident in the
pancreas since keratin-deficient mice cope well with pancreatitis
models. To further study the roles of keratins in the exocrine pancreas,
we used coxsackievirus B4-models, CVB4-V and CVB4-P, to induce severe
acute/chronic pancreatitis and acute pancreatitis, respectively, in
K8-null (which lack acinar keratins) and K18-null (which lack
cytoplasmic keratins) mice. Despite similar virus titers in all mice,
CVB4-V resulted in 40% mortality of the K8-null mice 14 days
post-infection compared to no lethality of WT and K18-null mice. In
contrast, K8-null mice were far less susceptible to CVB4-P-induced
damage as determined by histology and serology analysis, and they
recover faster than WT and K18-null mice. After CVB4 virus infection,
keratins aggregated during acinar degranulation, and K8/K18
site-specific phosphorylation was observed during degranulation and
recovery. Hence, keratins significantly affect CVB4 virulence,
positively or negatively, depending on the virus subtype and keratin makeup, in a virus replication-independent manner.


Nyckelord

Coxsackievirus, keratins, Pancreatitis

Senast uppdaterad 2019-07-12 vid 03:27