Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation

Liu, William J.1,2; Li, Jun3; Zou, Rongrong1; Pan, Jingcao3; Jin, Tao4,5; Li, Liqiang4; Liu, Peipei2; Zhao, Yingze2; Yu, Xinfen3; Wang, Haoqiu3; Liu, Guang4,5; Jiang, Hui4,5; Bi, Yuhai1,6,7; Liu, Lei1; Yuen, Kwok-Yung8,9; Liu, Yingxia1; Gao, George F.1,2,6,7

2020-09-22

10.1073/pnas.2013267117

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   影响因子和分区

0027-8424

Avian-origin influenza viruses overcome the bottleneck of the interspecies barrier and infect humans through the evolution of variants toward more efficient replication in mammals. The dynamic adaptation of the genetic substitutions and the correlation with the virulence of avian-origin influenza virus in patients remain largely elusive. Here, based on the one-health approach, we retrieved the original virus-positive samples from patients with H7N9 and their surrounding poultry/environment. The specimens were directly deep sequenced, and the subsequent big data were integrated with the clinical manifestations. Unlike poultry/environment-derived samples with the consistent dominance of avian signature 627E of H7N9 polymerase basic protein 2 (PB2), patient specimens had diverse ratios of mammalian signature 627K, indicating the rapid dynamics of H7N9 adaptation in patients during the infection process. In contrast, both human- and poultry/environment-related viruses had constant dominance of avian signature PB2-701D. The intrahost dynamic adaptation was confirmed by the gradual replacement of 627E by 627K in H7N9 in the longitudinally collected specimens from one patient. These results suggest that host adaptation for better virus replication to new hosts, termed "genetic tuning," actually occurred in H7N9-infected patients in vivo. Notably, our findings also demonstrate the correlation between rapid host adaptation of H7N9 PB2-E627K and the fatal outcome and disease severity in humans. The feature of H7N9 genetic tuning in vivo and its correlation with the disease severity emphasize the importance of testing for the evolution of this avian-origin virus during the course of infection.

host adaptation dynamic substitution next-generation sequencing H7N9 virus PB2-627

SCI

英语

NI期刊

第一 ; 通讯

Hangzhou Key Medicine Discipline Fund - Hangzhou government[20150733Q45] ; Shenzhen Science and Technology Research and Development Projects[JCYJ20150402111430617][JCYJ20151029151932602] ; Key Specialized Fund for New Infectious Diseases in Shenzhen City[201161] ; Excellent Young Scientist Program of the National Natural Science Foundation of China (NSFC)[81822040]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000575881900002

NATL ACAD SCIENCES

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;MATHEMATICS;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;PHARMACOLOGY & TOXICOLOGY;CHEMISTRY;PSYCHIATRY/PSYCHOLOGY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;AGRICULTURAL SCIENCES;ENGINEERING

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, State Key Discipline Infect Dis, Hosp 2,Shenzhen Key Lab Pathogen & Immun, Shenzhen 518112, Peoples R China
2.Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, NHC Key Lab Biosafety, Beijing 102206, Peoples R China
3.Hangzhou Ctr Dis Control & Prevent, Hangzhou 310021, Peoples R China
4.BGI Shenzhen, Shenzhen 518083, Peoples R China
5.BGI Shenzhen, China Natl GeneBank, Shenzhen 518083, Peoples R China
6.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
7.Chinese Acad Sci, Center Influenza Res & Early Warning, Beijing 100101, Peoples R China
8.Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China
9.Univ Hong Kong, Li Ka Shing Fac Med, HKU Shenzhen Hosp, Pokfulam, Hong Kong, Peoples R China

Liu, William J.,Li, Jun,Zou, Rongrong,et al. Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(38):23807-23814.

Liu, William J..,Li, Jun.,Zou, Rongrong.,Pan, Jingcao.,Jin, Tao.,...&Gao, George F..(2020).Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(38),23807-23814.

Liu, William J.,et al."Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.38(2020):23807-23814.