Perspective
Geographic Dependence, Surveillance, and Origins of the 2009 Influenza A (H1N1) Virus
N Engl J Med 2009; 361:115-119July 9, 2009
- Article
In April 2009, a new strain of human H1N1 influenza A virus was identified in Mexico. According to the World Health Organization (www.who.int/csr/don/2009_05_25), as of May 25, 2009, the virus had spread to 43 countries, with 12,515 reported cases and 91 associated deaths, and it has been assessed as having pandemic potential.1
Genomic analysis of the 2009 influenza A (H1N1) virus in humans indicates that it is closely related to common reassortant swine influenza A viruses isolated in North America, Europe, and Asia (Figure 1Figure 1
History of Reassortment Events in the Evolution of the 2009 Influenza A (H1N1) Virus.).2-4 The segments coding for the polymerase complex, hemagglutinin, nuclear protein, and nonstructural proteins show high similarity with the swine H1N2 influenza A viruses isolated in North America in the late 1990s (Table 1Table 1
Nucleotide Identities of Swine Influenza A Viruses Most Similar to the Ancestor of Segments 1, 2, 3, 4, 5, and 8 of the 2009 Swine-Origin Human Influenza A (H1N1) Virus.). H1N2 and other subtypes are descendants of the triple-reassortant swine H3N2 viruses isolated in North America. They have spread in swine hosts around the globe and have been found to infect humans.5 The segments coding for the neuraminidase and the matrix proteins of the new human H1N1 virus are, however, distantly related to swine viruses isolated in Europe in the early 1990s (Table 2Table 2
Nucleotide Identities of Swine Influenza A Viruses Most Similar to the Ancestor of Segments 6 and 7 of the 2009 Swine-Origin Human Influenza A (H1N1) Virus.). In particular, the closest isolated relatives of the neuraminidase segment have 94.4% similarity at the nucleotide level with European swine influenza A virus strains from 1992.In the past few years, there has been a worldwide effort to isolate and sequence the genomes of influenza A viruses, which has led to the depositing of more than 46,000 sequences in the Influenza Virus Resource of the National Center for Biotechnology Information (NCBI) (www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html). As of May 25, 2009, the NCBI database included sequences from more than 220 strains from the 2009 swine-origin human influenza A (H1N1) virus isolated at various sites around the world. Consequently, the origin and recent history of new strains can be inferred from study of the most similar deposited sequences. The percentage of matching nucleotides (the nucleotide identity) after nucleotide alignment, as determined with the use of the NCBI Basic Local Alignment Search Tool (BLAST) or other tools, is a common measure of similarity used by researchers in the field.
Figure 2Figure 2
Nucleotide Identities and Numbers of Years between Initial Isolations of Influenza A Viruses and Their Closest Relatives Deposited in the NCBI Database. shows the nucleotide identities and the numbers of years between the initial isolation of a given sequence of influenza A virus deposited in the NCBI database and the initial isolation of its closest relative. A total of 98% of all sequences of human influenza A viruses have relatives with at least 99% nucleotide identity, and 95% have a relative that was initially isolated within 2 years before their own first appearance. These numbers suggest that researchers have sampled human influenza A viruses efficiently — and point to a high degree of homogeneity among human influenza A viruses. Swine influenza A viruses have not been sampled as efficiently as human influenza A viruses; nevertheless, 86% of all segments from such strains have relatives with at least 99% nucleotide identity, and 71% have a relative that was initially isolated within 2 years before their own first appearance. Only 2% of all swine influenza A virus sequences have 94% nucleotide identity with their closest relative, and in 2% of cases, the closest relative appeared at least 20 years earlier.Figure 3Figure 3
Numbers of Sequences of Influenza A Viruses from Human and Swine Hosts Isolated on Various Continents and Deposited in the NCBI Database. shows the numbers of sequences from human and swine hosts isolated on various continents and deposited in the NCBI database. The numbers have increased dramatically over the past few years, and geography plays an important role. Most isolates of human influenza A viruses are from North America, Oceania, Asia, and Europe, and though there are many swine influenza A viruses from North America, Asia, and Europe, there are none from Africa, Oceania, or South America. North American and European swine influenza A (H1N1) viruses show strong geographic homogeneity, whereas some Asian isolates contain an admixture of both North American and European lineages (Figure 4Figure 4
Nucleotide Identities of Human and Swine Influenza A (H1N1) Viruses from within and outside North America, Europe, and Asia.). Although human influenza A viruses travel around the world with their hosts, swine viruses on different continents have largely distinct lineages.Given both the dependence of the distribution of swine influenza A viruses on geographic location and the lack of sampling in certain parts of the world, it is perhaps not surprising that the ancestors of the new human influenza A (H1N1) virus have gone unnoticed for almost two decades. Only more efficient surveillance could prevent such an event from happening in the future.
No potential conflict of interest relevant to this article has been reported.
This article (10.1056/NEJMp0904572) was published on May 27, 2009, at NEJM.org.
Source Information
From the Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics, Columbia University College of Physicians and Surgeons, New York.
- References
References
1
Fraser C, Donnelly CA, Cauchemez S, et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science 2009 May 14 (Epub ahead of print).
2
Trifonov V ,Khiabanian H ,Greenbaum B ,Rabadan R . The origin of the recent swine influenza A(H1N1) virus infecting humans. Euro Surveill 2009;14:pii=19193-pii=19193
Medline3
Novel Swine-Origin Influenza A (H1N1) Virus Investigation TeamEmergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605-2615
Full Text | Web of Science | Medline4
Garten RJ, Davis CD, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009 May 22 (Epub ahead of print).
5
Shinde V ,Bridges CB ,Uyeki TM , et al. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med 2009;360:2616-2625
Full Text | Web of Science | Medline
- Citing Articles (41)
Citing Articles
1
Panos Constantinides. (2012) Managing Crises in the Healthcare Service Chain. International Journal of Information Systems for Crisis Response and Management 2:4, 33-47
CrossRef2
Panos Constantinides. 2012. Managing Crises in the Healthcare Service Chain. , 229-244.
CrossRef3
Vuong N. Bui, Haruko Ogawa, Xininigen, Kazuji Karibe, Kengo Matsuo, Sanaa S.A. Awad, Germaine L. Minoungou, Satoshi Yoden, Hiroaki Haneda, Lai H. Ngo, Shio Tamaki, Yu Yamamoto, Kikuyasu Nakamura, Keisuke Saito, Yukiko Watanabe, Jonathan Runstadler, Falk Huettman, George M. Happ, Kunitoshi Imai. (2012) H4N8 subtype avian influenza virus isolated from shorebirds contains a unique PB1 gene and causes severe respiratory disease in mice. Virology 423:1, 77-88
CrossRef4
B. E. Pickett, E. L. Sadat, Y. Zhang, J. M. Noronha, R. B. Squires, V. Hunt, M. Liu, S. Kumar, S. Zaremba, Z. Gu, L. Zhou, C. N. Larson, J. Dietrich, E. B. Klem, R. H. Scheuermann. (2012) ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Research 40:D1, D593-D598
CrossRef5
S. Ansart. (2011) Infections respiratoires et voyages. La Revue de Médecine Interne 32, S213-S215
CrossRef6
Ping HUANG, Yuan-Sheng XU, Jing ZHONG, Han-Zhong NI, Yong-Hui ZHANG, Qiu-Xia CHEN, Song-Nuan TAN, Hui LI. (2011) Characterization of Epitope Peptides of Neuraminidases of The 2009 A H1N1 Viruses Designed by Immunoinformatics*. PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS 38:10, 929-935
CrossRef7
B. Pečavar, K. Nadrah, L. Papst, V. Čeč, T. Kotar, M. Matičič, J. Meglič-Volkar, L. Vidmar, B. Beović. (2011) Clinical characteristics of adult patients with influenza-like illness hospitalized in general ward during Influenza A H1N1 pandemic 2009/2010. Wiener klinische Wochenschrift 123:21-22, 662-667
CrossRef8
Philip Cooley, Shawn Brown, James Cajka, Bernadette Chasteen, Laxminarayana Ganapathi, John Grefenstette, Craig R. Hollingsworth, Bruce Y. Lee, Burton Levine, William D. Wheaton, Diane K. Wagener. (2011) The Role of Subway Travel in an Influenza Epidemic: A New York City Simulation. Journal of Urban Health 88:5, 982-995
CrossRef9
Remco Verdoold, Ron Gill, Felicia Ungureanu, Robert Molenaar, Rob P.H. Kooyman. (2011) Femtomolar DNA detection by parallel colorimetric darkfield microscopy of functionalized gold nanoparticles. Biosensors and Bioelectronics 27:1, 77-81
CrossRef10
Fuyan Sun, Yunzhi Zhang, Di Tian, Min Zheng, Li Liu, Renfang Zhang, Zhengsheng Dai, Jun Chen, Tingting Li, Hongzhou Lu. (2011) Responses after one dose of a monovalent influenza A (H1N1) 2009 inactivated vaccine in Chinese population—A practical observation. Vaccine 29:38, 6527-6531
CrossRef11
Laura Viviani, Baroukh M. Assael, Eitan Kerem. (2011) Impact of the A (H1N1) pandemic influenza (season 2009–2010) on patients with cystic fibrosis. Journal of Cystic Fibrosis 10:5, 370-376
CrossRef12
Hui Wang, Yi Wang, Wei Wang, Peng Fu, Peipei Liu, Weiming Zhu. (2011) Anti-influenza Virus Polyketides from the Acid-Tolerant Fungus Penicillium purpurogenum JS03-21. Journal of Natural Products110831103626094
CrossRef13
Chia-Wei Chang, Jiunn-Der Liao, Ai-Li Shiau, Chih-Kai Yao. (2011) Non-labeled virus detection using inverted triangular Au nano-cavities arrayed as SERS-active substrate. Sensors and Actuators B: Chemical 156:1, 471-478
CrossRef14
Mary C. Christman, Ambreen Kedwaii, Jianpeng Xu, Ruben O. Donis, Guoqing Lu. (2011) Pandemic (H1N1) 2009 virus revisited: An evolutionary retrospective. Infection, Genetics and Evolution 11:5, 803-811
CrossRef15
Gabriele Neumann, Yoshihiro Kawaoka. (2011) The first influenza pandemic of the new millennium. Influenza and Other Respiratory Viruses 5:3, 157-166
CrossRef16
Y. Sun, K. Qin, J. Wang, J. Pu, Q. Tang, Y. Hu, Y. Bi, X. Zhao, H. Yang, Y. Shu, J. Liu. (2011) High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses. Proceedings of the National Academy of Sciences 108:10, 4164-4169
CrossRef17
Amy J. Behrman. 2011. Health Hazards and Emergency Care for Health Care Workers. , 175-198.
CrossRef18
Rafal Tokarz, Vishal Kapoor, Winfred Wu, Joseph Lurio, Komal Jain, Farzad Mostashari, Thomas Briese, W Ian Lipkin. (2011) Longitudinal molecular microbial analysis of influenza-like illness in New York City, may 2009 through may 2010. Virology Journal 8:1, 288
CrossRef19
M. M. A. MAMUN, A. K. M. N. HUDA. (2011) Origins and Evolutionary Genomics of the Novel Swine-Origin Influenza A (H1N1) Virus in Humans —Past and Present Perspectives. YAKUGAKU ZASSHI 131:4, 553-562
CrossRef20
Wenjun Ma, Richard Oberst, Xi Li, Deborah Clouser, Richard Hesse, Raymond Rowland, Juergen A. Richt. (2010) Rapid detection of the pandemic 2009 H1N1 virus M gene by real-time and gel-based RT-PCR assays. Influenza and Other Respiratory Viruses 4:6, 397-403
CrossRef21
Zhen-peng Li, De-quan Ying, Peng Li, Fei Li, Xiao-chen Bo, Sheng-qi Wang. (2010) Analysis of synonymous codon usage bias in 09H1N1. Virologica Sinica 25:5, 329-340
CrossRef22
Guanghua Fu, Mengda Liu, Wenshu Zeng, Juan Pu, Yuhai Bi, Guangpeng Ma, Jinhua Liu. (2010) Establishment of a multiplex RT-PCR assay to detect different lineages of swine H1 and H3 influenza A viruses. Virus Genes 41:2, 236-240
CrossRef23
Joanne Embree. (2010) Pandemic 2009 (A)H1N1 influenza (swine flu) — the Manitoba experienceThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.. Biochemistry and Cell Biology 88:4, 589-593
CrossRef24
Michael W. Deem, Pooya Hejazi. (2010) Theoretical Aspects of Immunity. Annual Review of Chemical and Biomolecular Engineering 1:1, 247-276
CrossRef25
YePing Sun, Yi Shi, Wei Zhang, Qing Li, Di Liu, Christopher Vavricka, JingHua Yan, George F. Gao. (2010) In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009. Science China Life Sciences 53:6, 633-642
CrossRef26
C. F. N. Koegelenberg, E. M. Irusen, R. Cooper, A. H. Diacon, J. J. Taljaard, A. Mowlana, F. von Groote-Bidlingmaier, C. T. Bolliger. (2010) High mortality from respiratory failure secondary to swine-origin influenza A (H1N1) in South Africa. QJM 103:5, 319-325
CrossRef27
Y. P. Mu, Z. Y. Zhang, X. R. Chen, X. H. Xi, Y. F. Lu, Y. W. Tang, H. Z. Lu. (2010) Clinical features, treatments and prognosis of the initial cases of pandemic influenza H1N1 2009 virus infection in Shanghai China. QJM 103:5, 311-317
CrossRef28
Philippe R. S. Lagacé-Wiens, Ethan Rubinstein, Abba Gumel. (2010) Influenza epidemiology—past, present, and future. Critical Care Medicine 38, e1-e9
CrossRef29
Wai-Yip Lam, Ting-Fan Leung, Nelson Lee, Jo L.K. Cheung, Apple C.M. Yeung, Yolanda I.I. Ho, Rickjason C.W. Chan, Kitty S.C. Fung, Ian G. Barr, David S.C. Hui, Joseph J.Y. Sung, Paul K.S. Chan. (2010) Development and comparison of molecular assays for the rapid detection of the pandemic influenza A (H1N1) 2009 virus. Journal of Medical Virology 82:4, 675-683
CrossRef30
Elizabeth L. Daugherty, Richard D. Branson, Asha Deveraux, Lewis Rubinson. (2010) Infection control in mass respiratory failure: Preparing to respond to H1N1. Critical Care Medicine 38, e103-e109
CrossRef31
Amy L. Vincent, Kelly M. Lager, Kay S. Faaberg, Michelle Harland, Eraldo L. Zanella, Janice R. Ciacci-Zanella, Marcus E. Kehrli Jr, Bruce H. Janke, Alexander Klimov. (2010) Experimental inoculation of pigs with pandemic H1N1 2009 virus and HI cross-reactivity with contemporary swine influenza virus antisera. Influenza and Other Respiratory Viruses 4:2, 53-60
CrossRef32
Roberto Burioni, Filippo Canducci, Nicasio Mancini, Nicola Clementi, Monica Sassi, Donata De Marco, Roberta Antonia Diotti, Diego Saita, Michela Sampaolo, Giuseppe Sautto, Matteo Pianezze, Massimo Clementi. (2010) Monoclonal antibodies isolated from human B cells neutralize a broad range of H1 subtype influenza A viruses including swine-origin Influenza virus (S-OIV). Virology 399:1, 144-152
CrossRef33
Amy L. Vincent, Janice R. Ciacci-Zanella, Alessio Lorusso, Philip C. Gauger, Eraldo L. Zanella, Marcus E. Kehrli, Bruce H. Janke, Kelly M. Lager. (2010) Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1 influenza virus in pigs. Vaccine 28:15, 2782-2787
CrossRef34
Grant W. WATERER, David S. HUI, Christine R. JENKINS. (2010) Public health management of pandemic (H1N1) 2009 infection in Australia: A failure!. Respirology 15:1, 51-56
CrossRef35
Shuo Liu, Guangyu Hou, Qingye Zhuang, Yuelong Shu, Jiming Chen, Wenming Jiang, Jie Chen, Jinping Li. (2009) A SYBR Green I real-time RT-PCR assay for detection and differentiation of influenza A(H1N1) virus in swine populations. Journal of Virological Methods 162:1-2, 184-187
CrossRef36
Shobha Broor, Harendra Singh Chahar, Samander Kaushik. (2009) Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus. Indian Journal of Microbiology 49:4, 301-307
CrossRef37
Madhu Khanna, Binod Kumar, Neha Gupta, Prashant Kumar, Ankit Gupta, V. K. Vijayan, Harpreet Kaur. (2009) Pandemic swine influenza virus (H1N1): A threatening evolution. Indian Journal of Microbiology 49:4, 365-369
CrossRef38
Carlos F. Arias, Marina Escalera-Zamudio, María de los Dolores Soto-Del Río, Ana Georgina Cobián-Güemes, Pavel Isa, Susana López. (2009) Molecular Anatomy of 2009 Influenza Virus A (H1N1). Archives of Medical Research 40:8, 643-654
CrossRef39
Margaret C. Fisher. (2009) Novel H1N1 Pandemic. The Pediatric Infectious Disease Journal 28:10, 911-914
CrossRef40
Yonghui Zhang, Xiaojing Lin, Fengwei Zhang, Jia Wu, Wenjie Tan, Shengli Bi, Jianfang Zhou, Yuelong Shu, Yue Wang. (2009) Hemagglutinin and neuraminidase matching patterns of two influenza A virus strains related to the 1918 and 2009 global pandemics. Biochemical and Biophysical Research Communications 387:2, 405-408
CrossRef41
Antoinette J. Piaggio, Larry Clark, Alan B. Franklin, Sergios-Orestis Kolokotronis. (2009) Wild Bird’s-eye View of Influenza Virus A(H1N1) Phylogenetic Evolution. EcoHealth 6:3, 346-350
CrossRef
