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Title: Role of Viral Genetics in Dengue Epidemiological Fitness
Keywords: Dengue, Subgenomic RNA, Genetics, TRIM25, Epidemic
Issue Date: 16-Dec-2014
Source: GAYATHRI MANOKARAN (2014-12-16). Role of Viral Genetics in Dengue Epidemiological Fitness. ScholarBank@NUS Repository.
Abstract: The staggeringly large number of dengue virus (DENV) infections around the globe has led to increasing viral genetic diversity, some of which appears to be associated with greater epidemic potential. The underlying mechanisms of viral fitness in an epidemiological setting, however, remain poorly defined. We conducted in vitro studies and identified a determinant of fitness in a foreign dominant (PR-2B) DENV-2 clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic relative to genomic RNA during replication. The subgenomic RNA bound and inhibited de-ubiquitylation of tripartite motif 25 (TRIM25), which is needed to activate its E3 ligase activity critical for sustained and amplified RIG-I induced type-I interferon expression. Our findings demonstrate a unique viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness.
Appears in Collections:Ph.D Theses (Open)

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