References of "Kremer, Jacques R."
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See detailInterplay of measles virus with early induced cytokines reveals different wild type phenotypes.
Kessler, Julia UL; Kremer, Jacques R.; Muller, Claude P.

in Virus Research (2011), 155(1), 195-202

Differential effects of measles virus (MV) on the innate immune response may influence virus spread and severity of disease. Using a representative panel of 22 MV strains including 14 different genotypes ... [more ▼]

Differential effects of measles virus (MV) on the innate immune response may influence virus spread and severity of disease. Using a representative panel of 22 MV strains including 14 different genotypes, we found that wild-type (wt) differ considerably in their sensitivity to type I interferon (IFN). The wt virus production was 2-47-fold lower in IFN-alpha treated Vero/hSLAM cells, whereas vaccine virus production was reduced only 2-3-fold. Sequence analysis of the MV-P/C/V gene, revealed no obvious amino acid mutations that correlated with the different phenotypes. Strains also widely differed in their ability to induce type I IFN, tumor necrosis factor (TNF) alpha and other cytokines in human A549/hSLAM cells. Some wt strains that were highly sensitive to type I IFN induced only low levels of these and other cytokines. In vitro wt strains that produced the 5' copy-back defective interfering RNAs (5'cb-diRNA) characterized by Shingai et al. (2007), induced high levels of cytokines that otherwise were only reached by vaccine strains. These 5'cb-diRNAs emerged only in virus cultures during multiple passaging and were not detectable in clinical samples of measles patients. These subgenomic RNAs are an important confounding parameter in passaged wt viruses which must be carefully assessed in all in vitro studies. The present data show that MV wt strains differ in their sensitivity and their ability to temper with the innate immune response, which may result in differences in virulence. [less ▲]

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See detailRevealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.
Kessler, Julia UL; Kremer, Jacques R.; Shulga, Sergey V. et al

in Journal of Clinical Microbiology (2011), 49(2), 677-83

With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a ... [more ▼]

With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a virus using only this part of the genome. During outbreaks in Europe and Africa, we found MV strains with identical NP-HVR sequences. However, these strains showed considerable diversity within a larger sequencing window based on concatenated MV phosphoprotein and hemagglutinin genes (P/H pseudogenes). In Belarus, Germany, Russia, and the Democratic Republic of Congo, the P/H pseudogenes provided insights into chains of transmission, whereas identical NP-HVR provided none. In Russia, for instance, the P/H pseudogene identified temporal clusters rather than geographical clusters, demonstrating the circulation and importation of independent variants rather than large local outbreaks lasting for several years, as suggested by NP-HVR. Thus, by extending the sequencing window for molecular epidemiology, a more refined picture of MV circulation was obtained with more clearly defined links between outbreaks and transmission chains. Our results also suggested that in contrast to the P gene, the H gene acquired fixed substitutions that continued to be found in subsequent outbreaks, possibly with consequences for its antigenicity. Thus, a longer sequencing window has true benefits both for the epidemiological surveillance of measles and for the better monitoring of viral evolution. [less ▲]

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