Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Ruiz, Marie Christine; Díaz, Yuleima; Peña, Franshelle; Aristimuño, Olga Carolina; Chemello, María Elena; Michelangeli, Fabián A.

doi:10.1016/j.virol.2004.12.032

Cited by 27 publications

(37 citation statements)

References 39 publications

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“…So far, several reports have shown that Ca 2ϩ -dependent apoptosis occurs following infections with viruses (10) such as hepatitis C virus (3), human T-cell leukemia virus type 1 (57), HIV (25,26,31), and rotavirus (56). In addition to these findings, we show here that H5N1-AIV infection induced an influx of extracellular Ca 2ϩ , leading to apoptosis of DEF.…”

Section: Discussionsupporting

confidence: 81%

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Ueda

Daidoji²,

et al. 2010

J Virol

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In this study, we show that the highly pathogenic H5N1 avian influenza virus (AIV) . Thus, we investigated the molecular mechanisms of apoptosis induced by H5N1-AIV infection. Caspase-dependent and -independent pathways contributed to the cytopathic effects. We further showed that, in the induction of apoptosis, the hemagglutinin of H5N1-AIV played a major role and its cleavage sequence was not critical. We also observed outer membrane permeabilization and loss of the transmembrane potential of the mitochondria of infected DEF, indicating that mitochondrial dysfunction was caused by the H5N1-AIV infection. (

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Section: Discussionsupporting

confidence: 81%

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Ueda

Daidoji²,

et al. 2010

J Virol

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“…Further experiments, such as an evaluation of the NSP4 distribution within the cell in the absence of VP7, are required to differentiate between these possibilities. In a recent study, it was reported that rotavirus infection leads to a progressive depletion of ER pools released by agonists (32). Interestingly, in this work, such depletion was still observed when NSP4 was silenced, suggesting that this protein is not directly responsible for this effect.…”

Section: Discussionmentioning

confidence: 52%

“…It has recently been shown that in tunicamycin-treated, rotavirus-infected cells, the changes in Ca 2ϩ permeability of the plasma membrane are inhibited, thus suggesting that a glycosylated viral product, NSP4 or VP7, is responsible for such changes (32). NSP4 appears as a most likely candidate, given its several effects in Ca 2ϩ homeostasis.…”

Section: Rotavirus Infection Of Cells In Culture Induces Major Changementioning

confidence: 99%

“…Cell suspensions were incubated with 10 M fura-2 AM with Pluronic (2%) for 30 min, washed twice with PBS by centrifugation, resuspended in the medium described above, and maintained at room temperature until used. Intracellular Ca 2ϩ measurements were taken as previously described (32). Briefly, aliquots of the cell suspensions were washed and resuspended in the same medium but without albumin.…”

Section: Cell Cultures and Virus Infectionsmentioning

confidence: 99%

“…2A). Ca 2ϩ entry in rotavirus-infected cells is due to the activation of the virus-induced pathway plus an additional cellular component, called capacitative Ca 2ϩ entry, through store-operated channels located at the plasma membrane (6,32). Ca 2ϩ entry observed in mock-infected cells is mostly due in this case to the capacitative pathway.…”

Section: Effect Of Silencing Rotavirus Gene Expression On Changes Inmentioning

confidence: 99%

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Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca ²⁺ Homeostasis Induced by Infection of Cultured Cells

Zambrano¹,

Díaz

Peña

et al. 2008

J Virol

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Rotavirus infection of cells in culture induces major changes in Ca2؉ homeostasis. These changes include increases in plasma membrane Ca 2؉ permeability, cytosolic Ca 2؉ concentration, and total cell Ca 2؉ content and a reduction in the amount of Ca 2؉ released from intracellular pools sensitive to agonists. Various lines of evidence suggest that the nonstructural glycoprotein NSP4 and possibly the major outer capsid glycoprotein VP7 are responsible for these effects. In order to evaluate the functional roles of NSP4 and other rotavirus proteins in the changes in Ca 2؉ homeostasis observed in infected cells, the expressions of NSP4, VP7, and VP4 were silenced using the short interfering RNA (siRNA) technique. The transfection of specific siRNAs resulted in a strong and specific reduction of the expression of NSP4, VP7, and VP4 and decreased the yield of new viral progeny by more than 90%. Using fura-2 loaded cells, we observed that knocking down the expression of NSP4 totally prevented the increase in Ca 2؉ permeability of the plasma membrane and cytosolic Ca 2؉ concentration measured in infected cells. A reduction in the levels of VP7 expression partially reduced the effect of infection on plasma membrane Ca 2؉ permeability and Ca 2؉ pools released by agonist (ATP). In addition, the increase of total Ca 2؉ content (as measured by 45 Ca 2؉ uptake) observed in infected cells was reduced to the levels in mock-infected cells when NSP4 and VP7 were silenced. Finally, when the expression of VP4 was silenced, none of the disturbances of Ca 2؉ homeostasis caused by rotaviruses in infected cells were affected. These data altogether indicate that NSP4 is the main protein responsible for the changes in Ca 2؉ homeostasis observed in rotavirus-infected cultured cells. Nevertheless, VP7 may contribute to these effects. Viral-associated diarrhea remains one of the most common causes of morbidity and mortality among infants and young children. Worldwide estimations indicate that rotaviruses are the leading viral agent associated with severe diarrhea in children younger than 5 years old (20). In addition, rotavirus infections are also a main cause of diarrhea in calves, piglets, and the young of other animals of economic importance (20). Thus, further knowledge of the virus-cell interactions and the events leading to pathogenesis are necessary to improve or develop new strategies that may prevent or reduce the health and economic impact caused by rotavirus infections.Rotaviruses are members of the Reoviridae family. The rotavirus virion is icosahedral, nonenveloped, and composed of three concentric layers of proteins and a genome of 11 segments of double-stranded RNA. Each genomic segment, with the exception of segment 11, encodes one viral protein for a total of six structural (VP1 to VP7) and six nonstructural proteins (NSP1 to NSP6). The inner layer of the virion is formed by VP2 and also contains the RNA-dependent RNA polymerase VP1 and the guanylyltransferase/methylase VP3. The middle capsid is composed of the major virion...

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Evaluation of a bivalent recombinant vaccine candidate targeting norovirus and rotavirus: Antibodies to rotavirus NSP4 exert antidiarrheal effects without virus neutralization

Cao

Luan

et al. 2022

Journal of Medical Virology

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We previously found that when tandemly expressed with S R69A -VP8*, nonstructural protein 4 (NSP4) of the rotavirus Wa strain exerts a minor effect on elevating the antibody responses targeting the rotavirus antigen VP8* of the 60-valent nanoparticle S R69A -VP8* but could fully protect mice from diarrhea induced by the rotavirus strain Wa. In this study, we chose comparably less immunogenic norovirus 24-valent P particles with homogenous (i.e., VP8* from rotavirus) and heterogeneous (i.e., protruding domain of norovirus) antigens and in more challenging rotavirus SA11 strain-induced diarrhea mouse models to evaluate its main role in recombinant gastroenteritis virusspecific vaccines. The results showed that although as an adjuvant NSP4 exerted limited effects on the elevation of norovirus-specific or VP8*-specific neutralizing antibody production, as an antigen it could confer potent protection, particularly when synergized with VP8*, in rotavirus SA11 strain-induced diarrhea mouse models, possibly blocking the invasion of the intestinal wall by enterotoxin. NSP4 may be unnecessary for other recombinant vaccines as adjuvants, and its display mode should be evaluated specifically to avoid blocking coexpressed antigens in the norovirus P particles.

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Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Cited by 27 publications

References 39 publications

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca ²⁺ Homeostasis Induced by Infection of Cultured Cells

Evaluation of a bivalent recombinant vaccine candidate targeting norovirus and rotavirus: Antibodies to rotavirus NSP4 exert antidiarrheal effects without virus neutralization

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Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Cited by 27 publications

References 39 publications

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca 2+ Influx, Leading to Apoptosis in Avian Cells

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca 2+ Influx, Leading to Apoptosis in Avian Cells

Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca 2+ Homeostasis Induced by Infection of Cultured Cells

Evaluation of a bivalent recombinant vaccine candidate targeting norovirus and rotavirus: Antibodies to rotavirus NSP4 exert antidiarrheal effects without virus neutralization

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Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Highly Pathogenic H5N1 Avian Influenza Virus Induces Extracellular Ca ²⁺ Influx, Leading to Apoptosis in Avian Cells

Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca ²⁺ Homeostasis Induced by Infection of Cultured Cells