Differences in the epidemiology and virology of mild, severe and fatal human infections with avian influenza A (H7N9) virus

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Abstract

A novel avian influenza A (H7N9) virus caused 5-10 % mild and 30.5 % fatal human infections as of December 10, 2015. In order to investigate the reason for the higher rate of fatal outcome of this infection, this study compared the molecular epidemiology and virology of avian influenza A (H7N9) viruses from mild (N = 14), severe (N = 50) and fatal (N = 35) cases, as well as from non-human hosts (N = 73). The epidemiological results showed that the average age of the people in the mild, severe and fatal groups was 27.6, 52 and 62 years old, respectively ( p < 0.001). Males accounted for 42.9 % (6/14), 58.0 % (29/50), and 74.3 % (26/35) of cases in the mild, severe and fatal group respectively ( p = 0.094). Median days from onset to start of antiviral treatment were 2, 5 and 7 days in the mild, severe and fatal group, respectively ( p = 0.002). The median time from onset to discharge/death was 12, 40 and 19 days in the mild, severe and fatal group, respectively ( p < 0.001). Analysis of whole genome sequences showed that PB2 (E627K), NA (R294K) and PA (V100A) mutations were markedly associated with an increased fatality rate, while HA (N276D) and PB2 (N559T) mutations were clearly related to mild cases. There were no differences in the genotypes, adaptation to mammalian hosts, and genetic identity between the three types of infection. In conclusion, advanced age and delayed confirmation of diagnosis and antiviral intervention were risk factors for death. Furthermore, PB2 (E627K), NA (R294K) and PA (V100A) mutations might contribute to a fatal outcome in human H7N9 infection.

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Most cited references 34

Record: found
Abstract: found
Article: not found

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

Rongbao Gao, Bin Cao, Yunwen Hu … (2013)

New England Journal of Medicine, 368(20), 1888-1897

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Record: found
Abstract: found
Article: not found

Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

Qun Li, Lei Zhou, Minghao Zhou … (2014)

New England Journal of Medicine, 370(6), 520-532

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Record: found
Abstract: found
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Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model.

Zejun Li, Hualan Chen, Peirong Jiao … (2005)

We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause disease in mice. In the present study, we explored the genetic basis of this change in host range by comparing two of the viruses that are genetically similar but differ in their ability to infect mice and have different pathogenicity in mice. A/duck/Guangxi/22/2001 (DKGX/22) is nonpathogenic in mice, whereas A/duck/Guangxi/35/2001 (DKGX/35) is highly pathogenic. We used reverse genetics to create a series of single-gene recombinants that contained one gene from DKGX/22 and the remaining seven gene segments from DKGX/35. We find that the PA, NA, and NS genes of DKGX/22 could attenuate DKGX/35 virus to some extent, but PB2 of DKGX/22 virus attenuated the DKGX/35 virus dramatically, and an Asn-to-Asp substitution at position 701 of PB2 plays a key role in this function. Conversely, of the recombinant viruses in the DKGX/22 background, only the one that contains the PB2 gene of DKGX/35 was able to replicate in mice. A single amino acid substitution (Asp to Asn) at position 701 of PB2 enabled DKGX/22 to infect and become lethal for mice. These results demonstrate that amino acid Asn 701 of PB2 is one of the important determinants for this avian influenza virus to cross the host species barrier and infect mice, though the replication and lethality of H5N1 influenza viruses involve multiple genes and may result from a constellation of genes. Our findings may help to explain the expansion of the host range and lethality of the H5N1 influenza viruses to humans.

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Author and article information

Contributors

Zhiruo Zhang: (+86) 15618977655 , zhangzhiruo@sjtu.edu.cn

Shelan Liu: (+86) 571-87115137 , liushelan@126.com , liushelan@gmail.com

Journal

Journal ID (nlm-ta): Arch Virol

Journal ID (iso-abbrev): Arch. Virol

Title: Archives of Virology

Publisher: Springer Vienna (Vienna )

ISSN (Print): 0304-8608

ISSN (Electronic): 1432-8798

Publication date (Electronic): 18 February 2016

Publication date (Print): 2016

Volume: 161

Issue: 5

Pages: 1239-1259

Affiliations

[1 ]Department of Gastroenterology, The 421 Hospital of Chinese People’s Liberation Army, Guangzhou, People’s Republic of China

[2 ]Department of Senior Cadres, The 421 Hospital of Chinese People’s Liberation Army, Guangzhou, People’s Republic of China

[3 ]Pharmacy Department, The 421 Hospital of Chinese People’s Liberation Army, Guangzhou, People’s Republic of China

[4 ]GRID grid.452555.6, ISNI 0000000417583222, Department of Infectious Diseases, , Jinhua Municipal Central Hospital, ; Jinhua, People’s Republic of China

[5 ]GRID grid.412465.0, Department of Respiratory Medicine, , Second Affiliated Hospital of Zhejiang University, School of Medicine, ; Hangzhou, People’s Republic of China

[6 ]GRID grid.13402.34, ISNI 000000041759700X, Department of Oncology, Second Affiliated Hospital, School of Medicine, , Zhejiang University, ; Hangzhou, People’s Republic of China

[7 ]GRID grid.16821.3c, ISNI 0000000403688293, School of Public Health, , Shanghai Jiao Tong University, ; 227 South Chongqing Road, Huangpu District, Shanghai, 200025 People’s Republic of China

[8 ]GRID grid.198530.6, ISNI 0000000088032373, Department of Infectious Diseases, , Zhejiang Provincial Centre for Disease Control and Prevention, ; 3399 Binsheng Road, Binjiang District, Hangzhou, 310051 Zhejiang Province People’s Republic of China

Article

Publisher ID: 2781

DOI: 10.1007/s00705-016-2781-3

PMC ID: 7101734

PubMed ID: 26887968

SO-VID: da5dea48-d519-4f6d-b044-bec779919010

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.