How do host restriction factors influence dengue virus replication?

FEDERICO GIOVANNONI; PETER HEMMERICH; GARCÍA, CYBELE C

FUTURE VIROLOGY

FUTURE MEDICINE LTD

Lugar: Londres; Año: 2016

1746-0794

Dengue virus (DENV 1?4) is a majoremerging arthropod-borne pathogen,endemic to the tropical and subtropicalregions of the world, and infecting390 million individuals annually. DENVinfections can either proceed withoutsymptoms, resulting in self-limited denguefever, or, as increasingly reported, candevelop more severe manifestations inpatients, such as dengue hemorrhagic feverand dengue shock syndrome.Considerable breakthroughs have beenmade in recent years in the understandingof the structure of DENV particles, lifecycle and disease pathogenesis. However,despite the identification of many host andviral factors that either promote or protectthe host from severe symptoms of thedisease, both the complex nature of theirmutual interactions during natural infection,along with the absence of a suitableanimal model makes it difficult to fullyunderstand the pathogenesis of severe andfatal cases.A significant effort is being made by thescientific community to understand therole of each particular molecule within thecomplex network of interactions existingbetween host and viral factors. The mostcommon experimental approaches to elucidatethe function of a molecule are either todeplete it by blocking the expression of itsgene or to alter its activity by introducingloss-of-function mutations. Due to theirhigh efficiency and efficacy and low costcompared with other techniques, highthroughputgenome-wide RNAi screeningapproaches are the most powerful tools forthe identification of host factors and pathwaysinvolved in any step of a viral replicationcycle. Upon depletion of a particularhost cell factor, virus multiplication can beeither reduced or increased. Thus, accordingto the loss-of-function phenotype,host factors are classified either as pro- oranti-viral host factors.