serotype
not annotated - annotated - LINNAEUS only
20719250
Regulation of virulence factors, carbon utilization and virulence by SNF1 in Cryptococcus neoformans JEC21 and divergent actions of SNF1 between cryptococcal strains.
We describe here the functions of a Snf1/AMPK homolog in the human pathogenic yeast Cryptococcus neoformans, strain JEC21. We found that JEC21 SNF1 is a key regulator for the biosynthesis of the major virulence factors, stress resistance and alternative carbon source utilization. Disruption of JEC21 SNF1 results in defects of laccase activity and capsule production, sensitivity to cation stress. Especially, we found that JEC21 SNF1 is essential for growth at elevated temperature and for thermotolerance. To our knowledge, a role for Snf1 proteins in thermotolerance has not been reported. Furthermore, we observed a functional divergence between JEC21 SNF1 and its equivalent from serotype A strain H99. A high temperature is needed for H99 SNF1 to function in stress response and carbon source preference, but not for the JEC21 SNF1. Our results confirmed a critical role of JEC21 SNF1 in regulation of stress response and virulence. Revelation of divergent actions of SNF1 may help to understand the evolution of cryptococcal pathogenesis and provides insights into the strain-associated biosynthesis of virulence factors.
20962088
Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors.
The innate immune pathways that contribute to the potent immunogenicity of recombinant adenovirus (rAd) vaccine vectors remain largely undefined. Previous studies assessing innate immunity triggered by vaccine vectors have largely focused on in vitro studies involving antigen-presenting cells and on early in vivo inflammatory responses. Here, we systematically explore the Toll-like receptor (TLR) signaling requirements for the generation of cellular immune responses by intramuscular immunization with common and alternative serotype rAd vectors in mice. Antigen-specific CD8(+) T-lymphocyte responses elicited by these rAd vectors were significantly diminished in MyD88(-/-) mice but not in TRIF(-/-) or TLR3(-/-) mice, suggesting the importance of MyD88-dependent TLR signaling. However, the absence of each individual TLR resulted in minimal to no effect on vaccine-elicited cellular immune responses. Moreover, responses were not diminished in IL-1R(-/-) or IL-18R(-/-) mice. These data suggest that rAd vectors engage multiple MyD88-dependent signaling pathways, none of which are individually critical; rather, they are integrated to contribute to the potent immunogenicity of rAd vectors. Stimulation of multiple innate immune mechanisms may prove a generalizable property of potent vaccines, and this strategy could be harnessed in the development of next-generation vaccine vectors and adjuvants.
21029752
Multiplex PCR for rapid detection of serotype A foot-and-mouth disease virus variants with amino acid deletion at position 59 of the capsid protein VP3.
In India, there has been co-circulation, extinction and emergence of genotypes/lineages within serotype A foot-and-mouth disease (FMD) virus. At present an antigenically heterogeneous, unique lineage within genotype VII dominates the field outbreaks. This genetic cluster has amino acid deletion at position 59 of VP3 (VP3(59)-deletion group), considered to be critical antigenically. The emergence of this group warrants rapid and accurate detection to facilitate early planning and implementation of an effective control policy. A rapid multiplex PCR assay was developed for detection of the dominating VP3(59)-deletion group with 100% sensitivity and specificity, even before generating sequence data and confirmatory phylogenetic analysis. This development is important for surveillance of FMD in India.
20980526
An in-depth analysis of original antigenic sin in dengue virus infection.
The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.
21067947
Characterizing the role of RNA silencing components in Cryptococcus neoformans.
The RNA interference (RNAi) mediated by homology-dependent degradation of the target mRNA with small RNA molecules plays a key role in controlling transcription and translation processes in a number of eukaryotic organisms. The RNAi machinery is also evolutionarily conserved in a wide variety of fungal species, including pathogenic fungi. To elucidate the physiological functions of the RNAi pathway in Cryptococcus neoformans that causes fungal meningitis, here we performed genetic analyses for genes encoding Argonaute (AGO1 and AGO2), RNA-dependent RNA polymerase (RDP1), and Dicers (DCR1 and DCR2) in both serotype Aserotype A and D C. neoformans. The present study shows that Ago1, Rdp1, and Dcr2 are the major components of the RNAi process occurring in C. neoformans. However, the RNAi machinery is not involved in regulation of production of two virulence factors (capsule and melanin), sexual differentiation, and diverse stress response. Comparative transcriptome analysis of the serotype A and D RNAi mutants revealed that only modest changes occur in the genome-wide transcriptome profiles when the RNAi process was perturbed. Notably, the serotype D rdp1Delta mutants showed an increase in transcript abundance of active retrotransposons and transposons, such as T2 and T3, the latter of which is a novel serotype D-specific transposon of C. neoformans. In a wild type background both T2 and T3 were found to be weakly active mobile elements, although we found no evidence of Cnl1 retrotransposon mobility. In contrast, all three transposable elements exhibited enhanced mobility in the rdp1Delta mutant strain. In conclusion, the RNAi pathway plays an important role in controlling transposon activity and genome integrity of C. neoformans.
21492929
Serotype replacement in disease after pneumococcal vaccination.
Vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of pneumococcal disease and has had an important public health benefit. Because this vaccine targets only seven of the more than 92 pneumococcal serotypes, concerns have been raised that non-vaccine serotypes (NVTs) could increase in prevalence and reduce the benefits of vaccination. Indeed, among asymptomatic carriers, the prevalence of NVTs has increased substantially, and consequently, there has been little or no net change in the bacterial carriage prevalence. In many populations, pneumococcal disease caused by NVT has increased, but in most cases this increase has been less than the increase in NVT carriage. We review the evidence for serotype replacement in carriage and disease, and address the surveillance biases that might affect these findings. We then discuss possible reasons for the discrepancy between near-complete replacement in carriage and partial replacement for disease, including differences in invasiveness between vaccine serotypes. We contend that the magnitude of serotype replacement in disease can be attributed, in part, to a combination of lower invasiveness of the replacing serotypes, biases in the pre-vaccine carriage data (unmasking), and biases in the disease surveillance systems that could underestimate the true amount of replacement. We conclude by discussing the future potential for serotype replacement in disease and the need for continuing surveillance.