id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-341858-uz7vqq3r	Davis, C. Todd	Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness	2014-12-12		.txt	text/plain	4133	163	31	Influenza virus GOF studies have focused on several research areas: in vitro and/or in vivo replication in mammalian cell culture or animal hosts, adaptive mutations conferring changes in host susceptibility, alteration of receptor binding profiles and/or tropism for mammalian airway tissues, enhanced polymerase activity, changes in host antiviral response (e.g., cell signaling pathways), susceptibility to antiviral drugs, and pathogenesis and/or transmissibility in mammalian animal models. In both instances, molecularly based surveillance identified naturally occurring mutations in avian influenza viruses isolated from humans that had been demonstrated by GOF studies to increase transmissibility in the ferret model, prompting the public health actions described below. At the same time that increased case numbers were detected, public sequence database mining by researchers identified viruses from several 2013 human infections that possessed the same mutations shown by GOF studies to alter receptor-binding specificity toward an ␣2,6 preference (K189R and Q222L) and enhanced respiratory droplet transmission of a clade 1 virus in ferrets (N220K with Q222L) (42) .	./cache/cord-341858-uz7vqq3r.txt	./txt/cord-341858-uz7vqq3r.txt