Rotavirus infection induces an increase in intracellular calcium concentration in human intestinal epithelial cells: Role in microvillar actin alteration
Jp. Brunet et al., Rotavirus infection induces an increase in intracellular calcium concentration in human intestinal epithelial cells: Role in microvillar actin alteration, J VIROLOGY, 74(5), 2000, pp. 2323-2332
Rotaviruses, which infect mature enterocytes of the small intestine, are re
cognized as the most important cause of viral gastroenteritis in young chil
dren. We have previously reported that rotavirus infection induces microvil
lar F-actin disassembly in human intestinal epithelial Caco-2 cells (N, Jou
rdan, J, P, Brunet, C, Sapin, A, Blais, J, Cotte Laffitte, F, Forestier, A,
M, Quero, G. Trugnant and A, L, Servin, J, Virol, 72:7228-7236, 1998), In
this study, to determine the mechanism responsible for rotavirus-induced F-
actin alteration, we investigated the effect of infection on intracellular
calcium concentration ([Ca2+](i)) in Caco-2 cells, since Ca2+ is known to b
e a determinant factor for actin cytoskeleton regulation. As measured by qu
in2 fluorescence, viral replication induced a progressive increase in [Ca2](i) from 7 h postinfection, which was shown to be necessary and sufficient
for microvillar F-actin disassembly, During the first hours of infection,
the increase in [Ca2+](i) was related only to an increase in Ca2+ permeabil
ity of plasmalemma, At a late stage of infection, [Ca2+](i) elevation was d
ue to both extracellular Ca2+ influx and Ca2+ release from the intracellula
r organelles, mainly the endoplasmic reticulum (ER), We noted that at this
time the [Ca2+](i) increase was partially related to a phospholipase C (PLC
)-dependent mechanism, which probably explains the Ca2+ release from the ER
, We also demonstrated for the first time that viral proteins or peptides,
released into culture supernatants of rotavirus-infected Caco-2 cells, indu
ced a transient increase in [Ca2+](i) of uninfected Caco-2 cells, by a PLC
dependent efflux of Ca2+ from the ER and by extracellular Ca2+ influx. Thes
e supernatants induced a Ca2+-dependent microvillar F-actin alteration in u
ninfected Caco-2 cells, thus participating in rotavirus pathogenesis.