Biomedical subjects

Aure Saulnier

Publications and source records attributed to Aure Saulnier.

4 recordsLinked to original sources

PubMed2006

Reduced apoptosis in human intestinal cells cured of persistent poliovirus infection.

Cells cured of persistent virus infection can be used to investigate cellular pathways of resistance to viral cytopathic effects. Persistent poliovirus (PV) infections were established in human intestinal Caco-2 cells, and spontaneously cured cell cultures were obtained. Two cell clones, cl6 and b13, cured of type 3 PV mutant infection and their parental Caco-2 cells were compared for susceptibility to PV infection, PV receptor CD155 expression, capacity to differentiate into polarized enterocytes, and PV-, staurosporine-, and actinomycin D-induced apoptosis. Our results strongly suggest that cells that are partially resistant to apoptosis can be selected during persistent virus infection.

Apoptosis↗

PubMed2005

Complete cure of persistent virus infections by antiviral siRNAs.

Small interfering RNAs (siRNAs) have been developed as antiviral agents for mammalian cells. The capacity of specific siRNAs to prevent virus infections has been demonstrated, and there is evidence that these new antiviral agents could have a partial therapeutic effect a few days after infection. We investigated the possibility of curing a persistent infection, several months after becoming established, using an in vitro model of persistent poliovirus (PV) infection in HEp-2 cells. Despite high virus titers and the presence of PV mutants, repeated treatment with a mixture of two siRNAs targeting both noncoding and coding regions, one of them in a highly conserved region, resulted in the complete cure of the majority of persistently infected cultures. No escape mutants emerged in treated cultures. The antiviral effect of specific siRNAs, consistent with a mechanism of RNA interference, correlated with a decrease in the amount of viral RNA, until its complete disappearance, resulting in cultures cured of virions and viral RNA.

Animals↗

PubMed2005

Silencing viruses by RNA interference.

Post-transcriptional gene silencing (PTGS) makes possible new approaches for studying the various steps of the viral cycle. Plus-strand RNA viruses appear to be attractive targets for small interfering RNAs (siRNAs), as their genome functions as both mRNA and replication template. PTGS creates an alternative to classic reverse genetics for viruses with either negative-strand or double-stranded RNA genomes and for those with a large genome. PTGS allows modification of the expression of a given cellular gene as a means to elucidate its role in the viral cycle and in virus-host cell interactions, and to investigate cellular pathways involved in viral pathogenesis. It also allows the creation of new animal models of human diseases. In addition, PTGS already appears to be a promising new therapeutic tool to fight viral multiplication and dissemination through the host and to prevent inflammation and virus-induced pathogenesis, including virus-induced tumorigenesis.

Animals↗

PubMed2004

Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells.

Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface.

Agammaglobulinemia↗