Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System

Abstract

Rotaviruses represent one of the most successful pathogens in the world, with high infectivity and efficient transmission between the young of many animal species, including humans. To overcome host defenses, rotaviruses have evolved a plethora of strategies to effectively evade the innate immune response, establish initial infection in the small intestine, produce progeny, and shed into the environment. Previously, studying the roles and relative contributions of specific rotaviral factors in innate immune evasion had been challenging without a plasmid-only reverse genetics system.

SPLASH: a statistical, reference-free genomic algorithm unifies biological discovery

“…The domains enriched over controls were rotavirus VP3 and NSP3 proteins (Figure S2A). These two proteins have roles in blocking host innate immunity 18 . Thus, variation in viral protein domains interacting with the immune system may be a recurring theme in SPLASH protein profiling of viral strains.…”

“…France, June, Day (18) France, June, Day ( 43) weighted by c j in [-1,1] and summed to yield the anchor statistic S. Finally, a p-value is computed utilizing classical concentration inequalities, which we correct for multiple hypothesis testing (with dependence) by constructing q-values using Benjamini-Yekutieli, a variant of Benjamini Hochberg testing which corrects for arbitrary dependence. B.…”

“…This should be thought of as studying an alternative where samples from c j = +1 have targets that are independent and identically distributed with mean (under f) of , and samples with c j = -1 have targets that are independent µ We performed SPLASH protein domain profiling in a dataset of virally enriched samples from breakthrough infections in patients that had been vaccinated against rotavirus; nearly all did have rotavirus infection, but some also had other coinfections 17 . The top domains were rotavirus VP3 (Rotavirus_VP3, 76 SPLASH hits vs 9 control hits) followed by rotavirus NSP3 (Rota_NSP3, 87 SPLASH vs 35 control hits), indicating that these rotavirus genes have sequences that vary significantly among these patients; they have roles in blocking host innate immunity 18 , and so may be under selective pressure for variation. Random c's can recover samplesheet c's.…”