The love-hate relationship between host proteins and viral RNAs.
Flaviviruses, such as dengue, yellow fever and Zika viruses, use many tools to counter the immune responses of their hosts. Among the most potent of these tools is a non-coding RNA called the subgenomic flaviviral RNA (sfRNA), which is produced from the viral genome by host exonucleases. The sfRNA interacts with host RNA binding proteins to cripple the innate immune system of the human host and the mosquito vector. We will present examples that elucidate the mechanisms by which this non-coding RNA interferes with human and mosquito immune mechanisms. In one example, we discovered how the interaction between sfRNA and human RNA binding proteins altered viral fitness and epidemic potential. 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 RNA (sfRNA) relative to genomic RNA during replication. Furthermore, the PR-2B sfRNA shows enhanced sequence-dependent binding and inhibition of deubiquitylation of tripartite motif 25 (TRIM25), which is needed to activate its E3 ligase activity critical for sustained and amplified
KEYWORDS & TOPICS
Dengue, yellow fever, Zika viruses, non-coding RNA.
Name: Mariano A. García Blanco MD PhD
Institution: Biochemistry and Molecular Biology University of Texas Medical Branch Galveston TX USA.
Name: Antonio Muro
Institution: Universidad de Salamanca.