Reviewers This informative article was reviewed by Prof Xiufan Liu (nominated

Reviewers This informative article was reviewed by Prof Xiufan Liu (nominated by Dr Purificacion Lopez-Garcia) and Prof Sandor Pongor. identification of a different closest precursor strain for the NA segment by Su who also reported a quick characterization without phylogenetic analysis [6]. We have examined the detailed phylogenetic relationship of the NA of this new strain (hereafter referred to as JS5-like (H10N9)) using a maximum-likelihood tree (employing a gamma-distributed HKY85 substitution model [8] and 1000-replicate bootstrapping [9]) using MAFFT [10], Jalview [11] and PhyML [12] (Figure?1A) and confirmed that this JS5-like N9 NA was indeed more closely related to the H7N9 outbreak sequences than the previously postulated closest KO14-like (H7N9) ancestor and the H11N9 or H2N9 strains listed by Lam Prof Xiufan Liu (nominated by Dr Purificacion Lopez-Garcia) General comment: Based on available sequences submitted to GenBank, buy 73069-13-3 the writers used different phylogenetic solutions to analyze the NA source of the book avian-origin H7N9 pathogen leading to recent human being outbreak in China, and confirmed that A/poultry/Jiangsu/RD5/2013(H10N9) may be the closest precursor stress for the NA section within the H7N9 pathogen and its own internal genes are closely linked to those of the presumed precursor for the HA section, A/duck/Zhejiang/12/2011(H7N3), 1st suggested by Su et buy 73069-13-3 al. The writers figured the resources of both HA and NA donors for the reassortant H7N9 pathogen are of local rather than migratory-bird source. The manuscript can be publishable after cautious revision. Specific remarks: 1. Based on the more recently PHF9 released paper in Character (Lam et al. The genesis and way to obtain the H7N9 influenza infections causing human infections in China, doi:10.1038/nature12515), the NA gene of H7N9 is more closely related to the NA gene from H11N9 and H2N9 viruses in migratory wild birds or H11N9 viruses in domestic ducks in China. Therefore, the phylogenetic analyses in Figure?1(A), S1-A and S1-B, S2-C should include N9 sequences from these strains to determine if A/chicken/Jiangsu/RD5/2013(H10N9) is the closest precursor strain. 2. In Figure?1(D), the authors propose a revised model for the reassortment pathway leading to the genesis of the novel avian-origin H7N9 virus: the reassortant H7N9 viruses of avian origin derive their internal genes from BJ16-like (H9N2) virus of wild bird. However, more recently, reports indicated that the novel H7N9 viruses with diverse genotypes were generated by sequential reassortments involving distinct H9N2 donor viruses in different hosts (Lam et al., The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature, 2013, doi:10.1038/nature12515; Wu et al. Sequential Reassortments Underlie Diverse H7N9 genotypes in China. Cell Host and Microbe, 2013. Therefore, Figure?1(D) should be revised. Authors Reply: Many thanks for pointing buy 73069-13-3 to these papers which have only been published after initial submission of our manuscript. We totally agree that in order to provide the best current state-of-the-art view of the H7N9 origins the newly reported sequences should be included in our analysis and we therefore did the additional work including sequences from both papers. It turns out buy 73069-13-3 that the Su et al. strain A/chicken/Jiangsu/RD5/2013(H10N9) we discuss here is still the closest NA precursor and the Lam et al. H11N9 and H2N9 strains are in-between the KO14-like (H7N9) and JS5-like (H10N9). Related to comment 2, as the dialogue on H9N2-produced inner sections isn’t the primary concentrate of the ongoing function, we have been citing Wu et al today. for information on this and also have revised Body also?1D to take into account the brand new findings of sequential reassortments from different hosts. Reviewer amount: 2 Prof Sandor Pongor This function by Lee et al. tries to patch together influenza strains that may explain emergence from the book H7N9 in China. That is very important subject at this time and the results and conclusions of the manuscript donate to our current knowledge of the problem. While this manuscript was under distribution, a new function was released in Character that addresses the genesis and way to obtain the H7N9 influenza viruses causing human infections in China (Lam et al. Nature. 2013 Aug.