Given the interconnected nature of our world today, emerging pathogens and pandemic outbreaks are an ever-growing threat to the health and economic stability of the global community. This is evident by the recent 2009 Influenza A (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global bioterrorism. Fortunately, the biomedical community has been able to rapidly generate sequence data so these pathogens can be readily identified. To date, however, the utilization of this sequence data to rapidly produce relevant experimental results or actionable treatments is lagging in spite of obtained sequence data. Thus, a pathogenic threat that has emerged and/or developed into a pandemic can be rapidly identified; however, translating this identification into a targeted therapeutic or treatment that is rapidly available has not yet materialized. This commentary suggests that the growing technology of DNA synthesis should be fully implemented as a means to rapidly generate in vivo data and possibly actionable therapeutics soon after sequence data becomes available. 1. Pandemic Viral Outbreaks Today, the ability to determine if an isolated viral outbreak could develop into a pandemic has been facilitated by efficient PCR and sequencing techniques to quickly identify and characterize the pathogen [1]. The prompt generation of sequence data from infected individuals has allowed for the identification of these emergent pathogens and for the Center for Disease Control (CDC) or World Health Organization (WHO) to determine if these emergent pathogens pose a pandemic threat. This determination is based on the early rate of infection, sequence data similarity, and virulence factor molecular markers [2, 3]. Take for example the recent pandemic of the 2009 H1N1 Influenza A virus (2009 H1N1) which was identified in Mexico and rapidly spread to other countries [4]. Sample isolation and sequencing provided for immediate analysis of the sequence data and determination of origin, strain, and genomic characteristics of the virus [5]. Thus, health agencies could hypothesize that indeed it was a threat to the global community given its antigenic novelty [6]. The CDC has estimated that the H1N1 pandemic infected between 47 to 81 million individuals [7]. The majority of individuals infected with 2009 H1N1 experienced mild disease symptoms, yet it was estimated that the disease accounted for nearly 9,820 deaths in the United States (US) alone [7]. Influenza virus is a continual threat as the cause of a pandemic outbreak given the ability of the virus to reassort
References
[1]
J. He, M. E. Bose, E. T. Beck et al., “Rapid multiplex reverse transcription-PCR typing of influenza A and B virus, and subtyping of influenza A virus into H1, 2, 3, 5, 7, 9, N1 (human), N1 (animal), N2, and N7, including typing of novel swine origin influenza A (H1N1) virus, during the 2009 Outbreak in Milwaukee, Wisconsin,” Journal of Clinical Microbiology, vol. 47, no. 9, pp. 2772–2778, 2009.
[2]
C. Fraser, C. A. Donnelly, S. Cauchemez et al., “Pandemic potential of a strain of influenza A (H1N1): early findings,” Science, vol. 324, no. 5934, pp. 1557–1561, 2009.
[3]
J. R. Coleman, “The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages,” Virology Journal, vol. 4, article 9, 2007.
[4]
CDC, “Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March- April 2009,” Morbidity and Mortality Weekly Report, vol. 58, pp. 463–466, 2009.
[5]
S. U. Schnitzler and P. Schnitzler, “An update on swine-origin influenza virus A/H1N1: a review,” Virus Genes, vol. 39, no. 3, pp. 279–292, 2009.
[6]
G. Neumann, T. Noda, and Y. Kawaoka, “Emergence and pandemic potential of swine-origin H1N1 influenza virus,” Nature, vol. 459, no. 7249, pp. 931–939, 2009.
[7]
CDC, CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, CDC—H1N1 General Info, Atlanta, Ga, USA, 2009.
[8]
D. A. Steinhauer and J. J. Skehel, “Genetics of influenza viruses,” Annual Review of Genetics, vol. 36, pp. 305–332, 2002.
[9]
J. Lu, D. Liu, W. Liu, T. Shi, Y. Tong, and W. Cao, “Genetic stability and linkage analysis of the 2009 influenza A(H1N1) virus based on sequence homology,” Archives of Virology, vol. 154, no. 12, pp. 1883–1890, 2009.
[10]
R. J. Garten, C. T. Davis, C. A. Russell et al., “Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans,” Science, vol. 325, no. 5937, pp. 197–201, 2009.
[11]
C. J. Russell and R. G. Webster, “The genesis of a pandemic influenza virus,” Cell, vol. 123, no. 3, pp. 368–371, 2005.
[12]
T. G. Ksiazek, D. Erdman, C. S. Goldsmith et al., “A novel coronavirus associated with severe acute respiratory syndrome,” The New England Journal of Medicine, vol. 348, no. 20, pp. 1953–1966, 2003.
[13]
M. D. Wang and A. M. Jolly, “Changing virulence of the SARS virus: the epidemiological evidence,” Bulletin of the World Health Organization, vol. 82, no. 7, pp. 547–548, 2004.
[14]
D. Wang, L. Coscoy, M. Zylberberg et al., “Microarray-based detection and genotyping of viral pathogens,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15687–15692, 2002.
[15]
P. Elias, “Gene chip helps identify cause of mystery illness,” in Associated Press: USA Today, 2003.
[16]
K. V. Holmes, “Lai MMC,” in Fields' Virology, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 2001.
[17]
J. T. F. Lau, H. Tsui, M. Lau, and X. Yang, “SARS transmission, risk factors, and prevention in Hong Kong,” Emerging Infectious Diseases, vol. 10, no. 4, pp. 587–592, 2004.
[18]
J. T. F. Lau, X. Yang, H. Tsui, and E. Pang, “SARS preventive and risk behaviours of Hong Kong air travellers,” Epidemiology and Infection, vol. 132, no. 4, pp. 727–736, 2004.
[19]
T. M. Uyeki, “2009 H1N1 virus transmission and outbreaks,” The New England Journal of Medicine, vol. 362, no. 23, pp. 2221–2223, 2010.
[20]
D. A. Janies, I. O. Voronkin, J. Studer et al., “Selection for resistance to oseltamivir in seasonal and pandemic H1N1 influenza and widespread co-circulation of the lineages,” International Journal of Health Geographics, vol. 9, article 13, 2010.
[21]
L. V. Gubareva, R. G. Webster, and F. G. Hayden, “Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants,” Antimicrobial Agents and Chemotherapy, vol. 45, no. 12, pp. 3403–3408, 2001.
[22]
http://www.cdc.gov/flu/weekly/fluactivity.htm.
[23]
S. Mueller, J. R. Coleman, and E. Wimmer, “Putting synthesis into biology: a viral view of genetic engineering through de novo gene and genome synthesis,” Chemistry and Biology, vol. 16, no. 3, pp. 337–347, 2009.
[24]
S. M. Soto, “Human migration and infectious diseases,” Clinical Microbiology and Infection, vol. 15, supplement 1, pp. 26–28, 2009.
[25]
J. J. Amon, R. Devasia, G. Xia et al., “Molecular epidemiology of foodborne hepatitis A outbreaks in the United States, 2003,” Journal of Infectious Diseases, vol. 192, no. 8, pp. 1323–1330, 2005.
[26]
M. Varia, S. Wilson, S. Sarwal et al., “Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada,” Canadian Medical Association Journal, vol. 169, no. 4, pp. 285–292, 2003.
[27]
J. M. Drazen, “Smallpox and bioterrorism,” The New England Journal of Medicine, vol. 346, no. 17, pp. 1262–1263, 2002.
[28]
J. Nesmith, “SARS economic impact soared above health costs,” The Atlanta Journal-Constitution. In press.
[29]
R. D. Smith and T. Sommers, “Assessing the economic impact of public health emergencies in international concern: the case of SARS. Globalization, trade and heath working papers series,” Geneva, Switzerland, World Health Organization, 2003.
[30]
R. D. Smith, “Responding to global infectious disease outbreaks: lessons from SARS on the role of risk perception, communication and management,” Social Science and Medicine, vol. 63, no. 12, pp. 3113–3123, 2006.
[31]
M. I. Meltzer, N. J. Cox, and K. Fukuda, “The economic impact of pandemic influenza in the United States: priorities for intervention,” Emerging Infectious Diseases, vol. 5, no. 5, pp. 659–671, 1999.
[32]
W. McKibbin and D. Sidorenko, “Global macroeconomic consequences of pandemic influenza,” ACERH Research Forum, The University of Queensland Brisbane, 2006.
[33]
J. R. Coleman, D. Papamichail, S. Skiena, B. Futcher, E. Wimmer, and S. Mueller, “Virus attenuation by genome-scale changes in codon pair bias,” Science, vol. 320, no. 5884, pp. 1784–1787, 2008.
[34]
S. Mueller, J. R. Coleman, D. Papamichail et al., “Live attenuated influenza virus vaccines by computer-aided rational design,” Nature Biotechnology, vol. 28, no. 7, pp. 723–726, 2010.
[35]
E. Wimmer, S. Mueller, T. M. Tumpey, and J. K. Taubenberger, “Synthetic viruses: a new opportunity to understand and prevent viral disease,” Nature Biotechnology, vol. 27, no. 12, pp. 1163–1172, 2009.
[36]
H. Bügl, J. P. Danner, R. J. Molinari et al., “DNA synthesis and biological security,” Nature Biotechnology, vol. 25, no. 6, pp. 627–629, 2007.
[37]
GENEART, GENEART Synthesizes Genes for Swine Flu Vaccine in Record Speed, Munich Germany: GENEART, 2009.
[38]
S. S. Kim, L. F. Peng, W. Lin et al., “A cell-based, high-throughput screen for small molecule regulators of hepatitis C virus replication,” Gastroenterology, vol. 132, no. 1, pp. 311–320, 2007.
[39]
Y. S. Kim, Y. H. Lee, H. S. Kim et al., “Development of patatin knockdown potato tubers using RNA interference (RNAi) technology, for the production of human-therapeutic glycoproteins,” BMC Biotechnology, vol. 8, article 36, 2008.
[40]
A. P. McCaffrey, H. Nakai, K. Pandey et al., “Inhibition of hepatitis B virus in mice by RNA interference,” Nature Biotechnology, vol. 21, no. 6, pp. 639–644, 2003.
[41]
D. Palliser, D. Chowdhury, Q. Y. Wang et al., “An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection,” Nature, vol. 439, no. 7072, pp. 89–94, 2006.
[42]
A. V. Paul, E. Rieder, . Dong Wook Kim, J. H. Van Boom, and E. Wimmer, “Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg,” Journal of Virology, vol. 74, no. 22, pp. 10359–10370, 2000.
[43]
E. A. Emini, J. Leibowitz, and D. C. Diamond, “Recombinants of Mahoney and Sabin strain poliovirus type 1: analysis of in vitro phenotypic markers and evidence that resistance to guanidine maps in the nonstructural proteins,” Virology, vol. 137, no. 1, pp. 74–85, 1984.
[44]
N. De Jesus, D. Franco, A. Paul, E. Wimmer, and J. Cello, “Mutation of a single conserved nucleotide between the cloverleaf and internal ribosome entry site attenuates poliovirus neurovirulence,” Journal of Virology, vol. 79, no. 22, pp. 14235–14243, 2005.
[45]
J. Goudsmit, A. De Ronde, D. D. Ho, and A. S. Perelson, “Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase,” Journal of Virology, vol. 70, no. 8, pp. 5662–5664, 1996.
[46]
R. K. Naz and P. Dabir, “Peptide vaccines against cancer, infectious diseases, and conception,” Frontiers in Bioscience, vol. 12, no. 5, pp. 1833–1844, 2007.
[47]
W. Li, X. Hu, L. Liu, H. Chen, and R. Zhou, “Induction of protective immune response against Streptococcus suis serotype 2 infection by the surface antigen HP0245,” FEMS Microbiology Letters, vol. 2010, pp. 1574–6968, 2011.
[48]
T. H. Ottenhoff, T. M. Doherty, J. T. Dissel, et al., “First in humans: a new molecularly defined vaccine shows excellent safety and strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like responses,” Human Vaccines, vol. 6, no. 12, 2010.
[49]
C. Sun, Y. Zhang, Y. Liu, M. Zhang, and L. Chen, “Enhancement of immunogenicity of replication-defective adenovirus-based human immunodeficiency virus vaccines in rhesus monkeys,” AIDS Research and Human Retroviruses. In press.
[50]
C. Y. Teng, J. B. Millar, N. Grinshtein, J. Bassett, J. Finn, and J. L. Bramson, “T-cell immunity generated by recombinant adenovirus vaccines,” Expert Review of Vaccines, vol. 6, no. 3, pp. 347–356, 2007.
[51]
T. Shiratsuchi, U. Rai, A. Krause, S. Worgall, and M. Tsuji, “Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice,” Journal of Clinical Investigation, vol. 120, no. 10, pp. 3688–3701, 2010.
[52]
S. Mueller, E. Wimmer, and J. Cello, “Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event,” Virus Research, vol. 111, no. 2, pp. 175–193, 2005.
[53]
J. M. Coffin, “Attenuation by a thousand cuts,” The New England Journal of Medicine, vol. 359, no. 21, pp. 2283–2285, 2008.
