Expression of interferon α/β-induced antiviral genes in dendritic cells during dengue virus infection

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Expression of interferon α/β-induced antiviral genes in dendritic cells during dengue virus infection

 

Author: Chiu, Ka Yin Donna
Title: Expression of interferon α/β-induced antiviral genes in dendritic cells during dengue virus infection
Degree: M.Sc.
Year: 2014
Subject: Dengue.
Dengue viruses.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xiii, 84 leaves : color illustrations ; 30 cm
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2759002
URI: http://theses.lib.polyu.edu.hk/handle/200/7585
Abstract: Dengue virus infection is one of the public health issues in the tropical and subtropical regions affecting more than 100 countries and 50 million people annually. The disease could be asymptomatic or manifests as life-threatening conditions such as shock and hemorrhages. So far, neither effective vaccination nor treatment is available for dengue virus infections. Dengue is an arthropod-borne infection, which the dengue viruses (DENV) are believed to be maintained between mosquitoes and human in nature. Dendritic cells (DCs) are one of the primary targets for DENV upon the mosquito bite. Activation of the interferon α/β-induced antiviral genes in DCs upon DENV replication is critical for innate defense against the viral pathogen. This study aimed to investigate the expression of interferon α/β-induced antiviral genes in DCs upon DENV replication for a better understanding of antiviral responses. Besides, antiviral gene expressions were studied in two DC models, which were derived from primary human monocytes (IMMoDC) and myeloid leukaemia cell line MUTZ-3 (IMDC), in order to compare their suitability as an in-vitro model for studying DENV.
Using real-time PCR, expression patterns of the antiviral genes in IMMoDC were found to be different from those in IMDC. In IMMoDC, expression of 11 interferon α/β-induced antiviral genes, including three members of the IFIT family, MX1, MX2, ISG15 and CXCL10, peaked at 24 hours post-infection, the trends were similar to that of DENV replication. In IMDC, expression trends of six interferon α/β-induced antiviral genes, including TNFRSF9 and ISG20, were similar to the viral replication trend. The time course experiments showed possible correlation between the interferon α/β-induced antiviral genes expression and DENV-2 replication. Interestingly, HLA-C gene was down-regulated at 48 hour post-infection, such trend was more obvious in IMMoDC than IMDC. As HLA-C is involved in antigen presentation, down-regulation may favor host invasion. Besides, DENV replication levels were shown to be higher in IMMoDC than that in IMDC. The difference in viral replication patterns in the two in-vitro DC models suggested that the host-virus interaction may be different in IMMoDCs and IMDCs, and this needs further investigation.The pathogenesis of dengue virus infection is multifactorial and this makes the infectious disease pathogenesis difficult to be fully understood. This study may give evidence to the correlation in regulating interferon α/β-induced antiviral genes in host upon DENV-2 replication. Yet, the study may be affected by host factors included the donors variations in IMMoDC and insufficient understanding in the MUTZ-3 cell line, and viral factors included the effect of viral dose, viral strains, virulence and dengue serotypes (i.e. DENV-1 to -4). Further studies are of interest for investigating entire pathological mechanism of dengue infection in gaining better understanding.

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