NEJM - Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus - Article - April 11, 2013

[Farmer]

Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

Rongbao Gao, M.D., Bin Cao, M.D., Yunwen Hu, M.D., Zijian Feng, M.D., M.P.H., Dayan Wang, M.D., Wanfu Hu, M.D., Jian Chen, M.D., Zhijun Jie, M.D., Haibo Qiu, M.D., Ph.D., Ke Xu, M.D., Xuewei Xu, M.D., Hongzhou Lu, M.D., Ph.D., Wenfei Zhu, M.D., Zhancheng Gao, M.D., Nijuan Xiang, M.D., Yinzhong Shen, M.D., Zebao He, M.D., Yong Gu, M.D., Zhiyong Zhang, M.D., Yi Yang, M.D., Ph.D., Xiang Zhao, M.D., Lei Zhou, M.D., Xiaodan Li, M.D., Shumei Zou, M.D., Ye Zhang, M.D., Xiyan Li, M.D., Lei Yang, M.D., Junfeng Guo, M.D., Jie Dong, M.D., Qun Li, M.D., Libo Dong, M.D., Yun Zhu, M.D., Tian Bai, M.D., Shiwen Wang, M.D., Pei Hao, M.D., Weizhong Yang, M.D., Yanping Zhang, M.D., Jun Han, M.D., Hongjie Yu, M.D., Dexin Li, M.D., George F. Gao, Ph.D., Guizhen Wu, M.D., Yu Wang, M.D., Zhenghong Yuan, Ph.D., and Yuelong Shu, Ph.D.
April 11, 2013DOI: 10.1056/NEJMoa1304459

snip

The difference between the two Shanghai viruses and the similarity between the Shanghai/2 and Anhui/1 viruses argue against human-to-human transmission in these cases, and no close contacts of the patients have tested positive for these viruses. However, limited human-to-human transmission was observed in the H7 outbreak in the Netherlands in 200310; therefore, the pandemic potential of these novel avian-origin viruses should not be underestimated.

snip


Severe avian influenza A (H7N9) infections, characterized by high fever and severe respiratory symptoms, may pose a serious human health risk. We are concerned by the sudden emergence of these infections and the potential threat to the human population. An understanding of the source and mode of transmission of these infections, further surveillance, and appropriate counter measures are urgently required.

http://www.nejm.org/doi/full/10.1056/NEJMoa1304459?query=OF#t=article

[NS1]

Re: NEJM - Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus - Article - March 11, 2013

We are currently working to validate the claim in this paper of "mutation" at HA T160A. On page 1 in the "Abstract" section and the "Results" paragraph, we find the considerably perplexing statement:

A T160A mutation was identified at the 150-loop in the HA gene of all three viruses.

Our reference at amino position 160 was selected as Alanine due to the high frequency within H7N9 and ΣH7. While the Threonine value does occur in ΣH7 (minutely) and is found in other reservoirs (in passing, perhaps as some sort of host species transition toggle), our review shows no Threonine to support a reference level at aa160 in H3 Numbering? aa160 is active in many serotypes (H3N2, H5N1, H7N7, H9N2) and 160T does have a propensity toward mammalian-traited sequences (H3N2 canine & feline, H7N7 equine, H5N1 human-avian transition).

The authors of the NEJM article do mention the existence of unpublished sequences. Are these unpublished sequences the decision point for the Threonine reference? Although the "mutation" was noted in the Abstract, the HA revision was not mentioned in Table 2: Molecular Analysis of Three of the 2013 H7N9 Viruses, an exhibit displaying polymorphisms considered functionally important within certain gene segments.

At the moment, details concerning the genetics of the offending pathogen, including the Novel H7N9 HA Q226I adaptation arising at a critical Receptor Binding Site potentially from human H3N2, are available in the GeneWurx Cross Serotype Homology Analysis (Open-Access, Full-Text version). The genetics comparatives are under comprehensive discussion on the wider thread, entitled "China - H7N9 Human Isolates on Deposit at GISAID".

• GeneWurx Cross Serotype Homology Analysis, Open-Access, Full-Text version
• China - H7N9 Human Isolates on Deposit at GISAID, Comprehensive Genetics Discussion

A second paper refers to a T160A mutation?