Current Understanding of the Pathogenesis of Dengue Virus Infection
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REVIEW ARTICLE
Current Understanding of the Pathogenesis of Dengue Virus Infection Puneet Bhatt1 · Sasidharan Pillai Sabeena1 · Muralidhar Varma2 · Govindakarnavar Arunkumar1,3 Received: 18 June 2020 / Accepted: 4 November 2020 © The Author(s) 2020
Abstract The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. 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 antiDENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of crossreactive 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. Fcγ 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.
Introduction Dengue infection is a major public health problem and has been reported from the Americas, Africa, Southeast Asia, Europe, Western Pacific, and Eastern Mediterranean regions. This arboviral disease is found to be endemic in more than 100 countries and around 96 million infected individuals are symptomatic with varying levels of severity [1, 2]. Dengue * Puneet Bhatt [email protected] Sasidharan Pillai Sabeena [email protected] Muralidhar Varma [email protected] Govindakarnavar Arunkumar [email protected] 1
Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
2
Dept of Infectious Diseases, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka 576101, India
3
Present Address: WHO Country Office, Kathmandu, Nepal
is one of the leading causes of significant morbidity and economic burden in different regions across the world including Southeast Asia and the Indian subcontinent [3]. Dengue is a mosquito-borne Flavivirus infection, primarily transmitted by Aedes aegypti followed by Aedes albopictus mosquito and other species of genus Aedes [1, 4]. There are fo
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