The cellular immune response plays an important role in. This paper is an overview of the current understanding of the following mutually affected aspects. Dengue virus and the host innate immune response naoko uno1 and ted m. Elongated mitochondria make physical contacts with virus induced replication factories while mitochondriaassociated membranes are altered. Dengue feverdengue hemorrhagic fever dfdhf has emerged as the most important mosquitoborne viral diseases in tropical areas. Evolution of the innate and adaptive immune response in.
Reappearance of old viruses with higher mortality measles, flu association of viral infection with cancer. Mice were immunized with a single dose of infective dengue 2 virus and different markers of both branches of the induced adaptive immunity were measured. Viral innate immune evasion and the pathogenesis of. Dengue virus denv is a mosquitotransmitted single stranded rna virus. Pdf dengue virus denv is a mosquitoborne flavivirus that is endemic in many tropical and subtropical countries where the transmission. In order to study the interaction of dengue virus denv with the aedes aegypti immune response, we have characterized the denv infectionresponsive transcriptome of the immune competent a. Dengue virus denv is a mosquitoborne flavivirus that is endemic in many tropical and subtropical countries where the transmission vectors aedes spp. One most important question in dengue pathogenesis is the identity of cells that play a crucial role in antiviral innate immunity to dv at the early times of infection. Dengue virus replication in infected human keratinocytes. Dengue virus replication in infected human keratinocytes leads to activation of antiviral innate immune responses. Innate immune pathways important for dengue virus detection and protection. Secondary infection by a crossreactive serotype or virus challenges the host to produce an appropriate adaptive response based on memory of a different. We provide an overview of the mechanisms of immune sensing and functional immune responses that have been shown to aid clearance. Prime innate immune cells for dengue virus infection.
This study contributes to our understanding of dengue virus infection in aedes mosquitoes, which may aid towards the development of novel biocontrol strategies to halt dengue transmission. We also found that il1r1 is required for maximal irfdirected innate immune responses to inflammasomeactivating microbial products and dengue virus. Immune response to dengue virus and prospects for a. Vector competence and innate immune responses to dengue. Mathematical modeling and analysis of innate and humoral. Vectormediated transmission of denv is initiated when a bloodfeeding female aedes mosquito injects saliva, together with the virus, into the skin of its mammalian host. The battle between infection and host immune responses of. Evasion of the human innate immune system by dengue virus. Denv structure, viral infectivity, cellular receptors, innate immune response, and. Each serotype is antigenically different, meaning they elicit heterologous.
Aedes aegypti saliva enhances dengue virus infection of. Active innate immune response of the match system, response that helps antibodies and white blood cells eliminate the virus. Zika virus zikv is a flavivirus that is closely related to other human pathogens, such as dengue virus denv1. Pdf dengue virus and the host innate immune response. Dengue fever dengue hemorrhagic fever dfdhf has emerged as the most important mosquitoborne viral diseases in tropical areas. Ross1,2 abstract dengue virus denv is a mosquitoborne flavivirus that is endemic in many tropical and subtropical countries where the transmission vectors aedes spp.
Importantly, mitochondria elongation dampens the early interferon response in favor of virus. Reciprocal tripartite interactions between the aedes. Early cellular innate immune responses drive zika viral. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Dengue virus subverts host innate immunity by targeting adaptor protein mavs. Immune responses to dengue virus in the skin open biology. Dengue virus and the host innate immune response ncbi. An increased understanding of the adaptive immune response to natural dengue virus infection and candidate dengue vaccines has helped to define the specific antibody and t cell responses. Using primary human immune cells, our group investigates the contribution of dengue virus specific proteins to the evasion of innate immunity by this virus and the host factors that the virus interacts with in order to evade immune recognition and to establish infection in humans. The interplay between dengue virus and the human innate. Dengue virus denv is an arthropodborne single stranded rna virus of genus flavivirus. The upper panel shows the sensing of viral infection by rigi and cgas. Primary transmission usually involves aedes aegypti, which has expanded its. Dengue virus subverts host innate immunity by targeting adaptor.
Dengue is a major public health issue in tropical and subtropical regions worldwide. In the battle between a virus and its host, innate immunity serves as the first. Single cell immune profiling of dengue virus patients. Pdf inflammatory and innate immune responses in dengue. Article dengue virus perturbs mitochondrial morphodynamics to dampen innate immune responses graphical abstract highlights d denv ns4b induces mitochondria elongation during viral infection d elongated mitochondria and virus induced convoluted membranes are physically linked. Recruitment of cells that contribute to denv clearance is another important step in the containment of virus infection and initiation of adaptive immune responses, which occurs subsequent to the initial sentinel response of skinresident immune. The immunological and virological events that contribute to the establishment of zika virus zikv infection in humans are unclear. Here, we show that robust cellular innate immune responses.
As in mosquitoes, denv infection transcriptionally. We showed an intact response to new infection with zika virus which was enriched for early innate immune pathways and robust even during existing dengue infection. The four serotypes of dengue virus denv14 are spread primarily by aedes aegypti and ae. By a further analysis of the qualitative behavior of the quasisteady state, it was observed that innate immune response plays a pivotal role in dengue virus dynamics. Other potential strategies aim to manipulate characteristics such as vector competence vc, the innate capacity of the vector to transmit the virus. Even cellular targets of denv infection have important immune.
Dengue virus denv can inhibit both type i ifn production and signaling in susceptible human cells, including. Dengue virus inhibits immune responses in aedes aegypti cells. Serious disease can be seen during primary infection but is more frequent following second infection with a serotype different from that of a previous infection. Activation of the innate immune system including complement system, cytokine and chemokine responses at the early phase of denv infection plays a crucial role in response to the viruses and.
Dengue virus clearance by nk cells and skin homing t cells. A comparison was done assuming that innate immunity was active. Current advancements in dengue virus pathogenesis innate immune responses to dengue infections diagnosis and treatment of dengue this will. However, in a minority of primary infections a weakened innate immune response can result in more severe clinical signs. Understanding the role of skin immune cells in the activation of innate immunity to denv at the early times of infection is a.
Dengue virus perturbs mitochondrial morphodynamics to. The ability of many viruses to manipulate the host antiviral immune response often results in complex hostpathogen interactions. Dengue virus denv infection is the most prevalent mosquitoborne viral diseases in the world. Request pdf innate immune responses to dengue virus dengue fever dengue hemorrhagic fever dfdhf has emerged as the most important. The dengue virus dv has become endemic in most tropical urban centers throughout the world, and dhf has appeared concomitantly with this expansion.
Together with the innate and adaptive immune responses defuse illness of dengue and the individual will recover from dengue. Denvderived pamps are recognized by various pathogen. Omethyltransferase activity elicits a significant early innate immune response in host cells and thus replicates with. Conversely, dengue virus infection induces immune responses in the mosquito midgut tissue that act against the natural mosquito midgut microbiota. Dengue virus denv is a mosquitoborne member of the flavivirus genus and includes four serotypes denv1, denv2, denv3, and denv4, each of which is capable of causing dengue fever and dengue hemorrhagic fever dengue shock syndrome. The interplay between dengue virus and the human innate immune. Denv structure, viral infectivity, cellular receptors, innate immune response, and adaptive immunity. Innate immune responses to dengue virus request pdf. Can be activated rapidly and functions within hours of a viral infection. Innate immune responses to dengue virus sciencedirect. Indeed, dengue virus has many nonstructural proteins that allow the inhibition of various mediators of the innate immune system response. Innate antiviral immunity is the first line of defence against viral pathogens and participates in the establishment of the adaptive immune response. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity.
The four serotypes of dengue virus denv1denv4 are spread primarily by aedes aegypti and aedes albopictus mosquitoes, whose geographic range continues to expand. Denv infection in keratinocyte is a potent inducer of ifns surasombatpattana et al. Request pdf innate immune responses to dengue virus dengue feverdengue hemorrhagic fever dfdhf has emerged as the most important. The innate immune response, in addition to the b and tcell response, plays a role in protection against dengue virus denv infection and the degree of disease severity. Emerging concepts in dengue pathogenesis and host innate. The rapid initiation of innate host defense might be a limiting step of dv infection. Humans are the only host for epidemic strains of denv, and the virus has developed sophisticated mechanisms to evade human innate immune responses. To define the role of the cellular immune response in the protection against dengue, we selected the mouse encephalitis model. With dengue virus denv infection, its viral rna is recognized by the. These include innate immune responses such as production of type i and type ii interferons by the cells directly infected with denv, cell killing. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response. Adaptive immune responses to primary and secondary dengue virus. Thus, our study suggests that concurrent dengue infection would not be expected to impair immune responses to new infection with zika virus. Using primary human immune cells, our group investigates the contribution of dengue virus specific proteins to the evasion of innate immunity by this virus and the host factors that the virus.
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