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Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fc\u03b3 receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.<\/jats:p>","DOI":"10.1007\/s00284-020-02284-w","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:26:14Z","timestamp":1606177574000},"page":"17-32","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":342,"title":["Current Understanding of the Pathogenesis of Dengue Virus Infection"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-1443","authenticated-orcid":false,"given":"Puneet","family":"Bhatt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidharan Pillai","family":"Sabeena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidhar","family":"Varma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govindakarnavar","family":"Arunkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"issue":"8","key":"2284_CR1","volume":"6","author":"SR Mutheneni","year":"2017","unstructured":"Mutheneni SR, Morse AP, Caminade C, Upadhyayula SM (2017) Dengue burden in India: recent trends and importance of climatic parameters. 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