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Immunological serotype interactions and their effect on the epidemiological pattern of dengue.

ABSTRACT: Long-term epidemiological data reveal multi-annual fluctuations in the incidence of dengue fever and dengue haemorrhagic fever, as well as complex cyclical behaviour in the dynamics of the four serotypes of the dengue virus. It has previously been proposed that these patterns are due to the phenomenon of the so-called antibody-dependent enhancement (ADE) among dengue serotypes, whereby viral replication is increased during secondary infection with a heterologous serotype; however, recent studies have implied that this positive reinforcement cannot account for the temporal patterns of dengue and that some form of cross-immunity or external forcing is necessary. Here, we show that ADE alone can produce the observed periodicities and desynchronized oscillations of individual serotypes if its effects are decomposed into its two possible manifestations: enhancement of susceptibility to secondary infections and increased transmissibility from individuals suffering from secondary infections. This decomposition not only lowers the level of enhancement necessary for realistic disease patterns but also reduces the risk of stochastic extinction. Furthermore, our analyses reveal a time-lagged correlation between serotype dynamics and disease incidence rates, which could have important implications for understanding the irregular pattern of dengue epidemics.

SUBMITTER: Recker M

PROVIDER: S-EPMC2684681 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq.ResultsFour cDNA libraries were constructed, and 2428 differentially expressed genes (DEGs) of the host and 333 DEGs of App were detected. The host DEGs were mainly enriched in inflammatory signaling pathways, such as the TLR, NLR, RLR, BCR and TCR signaling pathways, resulting in large-scale cytokine up-regulation and thereby yielding a cytokine cascade for anti-infection and lung damage. The majority of the up-regulated cytokines are involved in the IL-23/IL-17 cytokine-regulated network, which is crucial for host defense against bacterial infection. The DEGs of App were mainly related to the transport and metabolism of energy and materials. Most of these genes are metabolic genes involved in anaerobic metabolism and important for challenging the host and adapting to the anaerobic stress conditions observed in acute hemorrhagic pneumonia. Some of these genes, such as adhE, dmsA, and aspA, might be potential virulence genes. In addition, the up-regulation of genes associated with peptidoglycan and urease synthesis and the restriction of major virulence genes might be immune evasion strategies of App. The regulation of metabolic genes and major virulence genes indicate that the dominant antigens might differ during the infection process and that vaccines based on these antigens might allow establishment of a precise and targeted immune response during the early phase of infection.ConclusionThrough an analysis of transcriptional data by dual RNA-seq, our study presents a novel global view of the interactions of App with its host and provides a basis for further study.

Project description:The Asian/American genotype of dengue virus serotype 2 (DENV-2) has been introduced in Brazil through the state of Rio de Janeiro around 1990, and since then it has been spreading and evolving, leading to several waves of dengue epidemics throughout the country that cause a major public health problem. Of particular interest has been the epidemic of 2008, whose highest impact was evidenced in the state of Rio de Janeiro, with a higher number of severe cases and mortality rate, compared to previous outbreaks. Interestingly, no circulation of DENV-2 was witnessed in this region during the preceding 9-year period. By early 2010, phylogenetic analysis of the 2008 epidemic strain revealed that the outbreak was caused by a new viral lineage of the Asian/American genotype, which was pointed as responsible for the outbreak severity as well. The same scenario is repeating in 2019 in this state; however, only a few cases have been detected yet. To provide information that helps to the understanding of DENV-2 dynamics in the state of Rio de Janeiro, and thereafter contribute to public health control and prevention actions, we employed phylogenetic studies combined with temporal and dynamics geographical features to determine the origin of the current viral strain. To this effect, we analyzed a region of 1626 nucleotides entailing the Envelope/NS1 viral genes. Our study reveals that the current strain belongs to the same lineage that caused the 2008 outbreak, however, it is phylogenetically distant from any Brazilian strain identified so far. Indeed, it seemed to be originated in Puerto Rico around 2002 and has been introduced into the state in late 2018. Taking into account that no DENV-2 case was reported over the last decade in the state (representing a whole susceptible children generation), and the fact that a new viral strain may be causing current dengue infections, these results will be influential in strengthening dengue surveillance and disease control, mitigating the potential epidemiological consequences of virus spread.

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Immunological serotype interactions and their effect on the epidemiological pattern of dengue.

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