RESUMO

The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR-2B) DENV serotype 2 (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 flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid-inducible gene 1 (RIG-I)-induced type I interferon expression. Our findings demonstrate a distinctive viral RNA-host protein interaction to evade the innate immune response for increased epidemiological fitness.

Assuntos

Vírus da Dengue/fisiologia , Dengue/imunologia , Dengue/virologia , Imunidade Inata , Interferon Tipo I/imunologia , RNA Viral/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Replicação Viral , Animais , Biodiversidade , Chlorocebus aethiops , Proteína DEAD-box 58 , RNA Helicases DEAD-box/metabolismo , Dengue/epidemiologia , Vírus da Dengue/genética , Humanos , Interferon Tipo I/antagonistas & inibidores , Interferon Tipo I/genética , Porto Rico/epidemiologia , RNA Viral/genética , Receptores Imunológicos , Proteínas com Motivo Tripartido , Ubiquitinação , Células Vero

Assuntos

Biotecnologia , Biotecnologia/normas , Porto Rico