



Study with the several resources on Docsity
Earn points by helping other students or get them with a premium plan
Prepare for your exams
Study with the several resources on Docsity
Earn points to download
Earn points by helping other students or get them with a premium plan
Community
Ask the community for help and clear up your study doubts
Discover the best universities in your country according to Docsity users
Free resources
Download our free guides on studying techniques, anxiety management strategies, and thesis advice from Docsity tutors
A comprehensive overview of the dengue virus (denv), including its classification, epidemiology, structure, pathogenesis, clinical manifestations, immune response, vaccine development, diagnostics, and treatment. It delves into the viral life cycle, immune evasion mechanisms, the role of the non-structural protein ns1, and the impact of host genetics on the immune response. The document also highlights emerging research topics, such as viral quasispecies, innate immune modulators, and therapeutic targets, as well as the challenges in vaccine development. Additionally, it touches on the global and public health perspectives, including epidemic prediction, response, and vector control innovations. This in-depth exploration of dengue virus can be valuable for students, researchers, and healthcare professionals interested in understanding the complexities of this significant global health concern.
Typology: Study notes
1 / 6
This page cannot be seen from the preview
Don't miss anything!
1. Introduction to Dengue Virus (DENV) Classification : o Family: Flaviviridae o Genus: Flavivirus o Four serotypes: DENV-1, DENV-2, DENV-3, DENV- Epidemiology : o Transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. o Found in tropical and subtropical regions around the world. o Approximately 390 million infections annually, with 96 million manifesting clinically. 2. Structure of Dengue Virus Genome : o Positive-sense single-stranded RNA (~10.7 kb). o Encodes a single polyprotein, cleaved into three structural (C, prM/M, E) and seven non-structural (NS) proteins. Viral Proteins : o Capsid (C) : Forms the viral nucleocapsid. o Membrane (prM/M) : Protects the E protein during assembly. o Envelope (E) : Major antigenic determinant; involved in viral attachment and entry into host cells. o NS Proteins : Key roles in replication (NS1, NS3, NS5) and immune evasion (NS1, NS2A). 3. Pathogenesis of Dengue Virus Viral Entry and Replication : o DENV enters host cells via receptor-mediated endocytosis, primarily in monocytes, dendritic cells, and endothelial cells. o The virus uncoats in the endosome, releasing RNA into the cytoplasm, where translation and replication occur. Immune Response : o Innate Immunity : Activation of pattern recognition receptors (PRRs) like TLR3, RIG-I, and MDA5, leading to the production of type I interferons. o Adaptive Immunity : Involves both humoral (antibodies) and cellular (T- cells) responses. o Antibody-Dependent Enhancement (ADE) : Non-neutralizing antibodies from a previous infection can enhance viral entry and replication in Fc receptor-bearing cells, leading to more severe disease.
4. Clinical Manifestations Dengue Fever (DF) : o Symptoms: High fever, severe headache, retro-orbital pain, myalgia, arthralgia, rash. o Typically self-limiting, but may progress to severe dengue. Severe Dengue (Dengue Hemorrhagic Fever/Dengue Shock Syndrome) : o Characterized by plasma leakage, severe bleeding, and organ impairment. o Pathophysiology: Increased vascular permeability, leading to hemoconcentration and potentially shock. 5. Immunopathogenesis Cytokine Storm : Overproduction of pro-inflammatory cytokines (IL-6, TNF-α, IL- 10) leading to systemic inflammation. Vascular Leakage : Mediated by immune complexes, complement activation, and inflammatory cytokines. Thrombocytopenia : Decreased platelet production and increased destruction; immune-mediated mechanisms. NS1 Protein : o Soluble NS1 contributes to endothelial dysfunction, complement activation, and vascular leakage. o Elicits a strong antibody response, but also involved in ADE and immune complex formation. 6. Host Immune Response Innate Immune Response : o Activation of PRRs, leading to IFN-α/β production and the antiviral state. o DENV evades immune detection by NS proteins interfering with signaling pathways (e.g., inhibition of IFN signaling by NS5). Adaptive Immune Response : o B cells : Production of antibodies against E and NS1 proteins. Memory B cells play a role in secondary infections. o T cells : CD4+ T cells produce cytokines; CD8+ T cells kill infected cells. Cross-reactive memory T cells may contribute to immunopathology. 7. Vaccine Development Challenges : o Four serotypes: Immunity to one serotype increases the risk of severe disease upon subsequent infection with another serotype due to ADE. o Balancing immune responses across all serotypes is critical. Current Vaccines : o Dengvaxia (CYD-TDV): First licensed vaccine; provides partial protection but may increase the risk of severe dengue in seronegative individuals. o Live-attenuated Vaccines : Under development, designed to induce balanced immunity to all four serotypes.
o The NS proteins, particularly NS3 (helicase/protease) and NS5 (RNA- dependent RNA polymerase), are crucial for viral RNA replication. o The viral RNA is replicated within the host cell's ER-derived membrane vesicles, forming double-stranded RNA intermediates. Assembly and Release: o Newly synthesized viral RNA is packaged into nucleocapsids, which are then enveloped by a membrane containing prM and E proteins. o Immature virions bud into the ER and are transported through the Golgi apparatus, where furin cleavage of prM to M results in mature virions. o Mature virions are released from the cell via exocytosis, ready to infect new cells.