Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation

Citation
Cl. Liao et al., Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation, J VIROLOGY, 75(17), 2001, pp. 7828-7839
Citations number
78
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022538X → ACNP
Volume
75
Issue
17
Year of publication
2001
Pages
7828 - 7839
Database
ISI
SICI code
0022-538X(200109)75:17<7828:SIFRIO>2.0.ZU;2-X
Abstract
Flaviviruses comprise a positive-sense RNA genome that replicates exclusive ly in the cytoplasm of infected cells. Whether flaviviruses require an acti vated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate n uclear factor kappa B (NF-kappaB), and salicylates have been shown to inhib it NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured ce lls. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated fl avivirus-triggered apoptosis. However, flavivirus replication was not affec ted by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhib itor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing I kappaB alpha-DeltaN, a dominant-negative mutant t hat antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cel ls, suggesting that NF-kappaB activation is not essential for either flaviv irus replication or flavivirus-induced apoptosis. Salicylates still diminis hed flavivirus replication and blocked apoptosis in the same I kappaB alpha -DeltaN cells. This inhibition of flaviviruses by salicylates could be part ially reversed by a specific p38 mitogen-activated protein (MAP) kinase inh ibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activi ty but is independent of blocking the NF-kappaB pathway.