Gain-of-Function Research and the Relevance to Clinical Practice

Journal of Infectious Diseases

Volumn 213, Issue 9, 2016, Pages 1364-1369

  Kilianski, Andy ^a   Nuzzo, Jennifer B ^b   Modjarrad, Kayvon ^c  

^a EDGEWOOD CHEMICAL BIOLOGICAL CENTER   (United States)

^b UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^c Walter Reed Army Institute for Research   (United States)

Author keywords

coronavirus; gain of function; health policy; influenza; potential pandemic pathogens; science policy

Indexed keywords

LIVE VACCINE;

AVIAN INFLUENZA VIRUS; CLINICAL PRACTICE; DISEASE SURVEILLANCE; DISEASE TRANSMISSION; GAIN OF FUNCTION RESEARCH; GENE MUTATION; GENE SEQUENCE; HEALTH CARE POLICY; HEALTH CARE SURVEY; HUMAN; INFLUENZA A VIRUS (H7N9); MEDICAL RESEARCH; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; NONHUMAN; PRIORITY JOURNAL; PUBLIC HEALTH; REVIEW; RISK BENEFIT ANALYSIS; SARS CORONAVIRUS; VIRAL TROPISM; VIRUS REPLICATION; ANIMAL; GENETICS; INFLUENZA A VIRUS; METHODOLOGY; MOUSE; MUTATION; PANDEMICS; PATHOGENICITY; RNA VIRUS INFECTIONS; STANDARDS; VIROLOGY;

ANIMALS; BIOMEDICAL RESEARCH; HEALTH POLICY; HUMANS; INFLUENZA A VIRUS; MICE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; MUTATION; PANDEMICS; RESEARCH DESIGN; RNA VIRUS INFECTIONS; SARS VIRUS;

EID: 84969987156     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiv473     Document Type: Review

References (50)

1. DuprexWP, Fouchier RAM, Imperiale MJ, LipsitchM, Relman DA. Gain-of-function experiments: time for a real debate. Nat Rev Microbiol 2014.
2. Department of Health and Human Services. US government gain-of-function deliberative process and research funding pause on selected gain-of-function research involving influenza, MERS, and SARS viruses, 2014. http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf. Accessed 6 October 2015.
3. Department of Health and Human Services. United States government policy for institutional oversight of life sciences dual use research of concern, 2014. http://www.phe.gov/s3/dualuse/documents/durc-policy.pdf. Accessed 6 October 2015.
4. Federal Select Agent Program, Centers for Disease Control and Prevention. Select agents and toxins list, 2014. http://www.selectagents.gov/SelectAgentsandToxins List.html. Accessed 6 October 2015.
5. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005; 437:889-93.
6. Tumpey TM. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005; 310:77-80.
7. van Aken J. Risks of resurrecting 1918 flu virus outweigh benefits. Nature 2006; 439:266.
8. Herfst S, Schrauwen EJA, Linster M, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012; 336:1534-41.
9. Imai M, Watanabe T, Hatta M, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012; 486:420-8.
10. National Institutes of Health. Press statement on the NSABB review of H5N1 research. NIH News Events, 2011. http://www.nih.gov/news/health/dec2011/od-20. htm. Accessed 6 October 2015.
11. National Science Advisory Board for Biosecurity. Full recommendations of NSABB regarding March 29-30, 2012 meeting to review revised manuscripts on transmissibility of A/H5N1, 2012. http://osp.od.nih.gov/sites/default/files/resources/03302012-NSABB-Recommendations-1.pdf. Accessed 6 October 2015.
12. Department of Health and Human Services (DHHS). the US government policy for oversight of life science dual use research of concern, 2012. http://osp.od. nih.gov/sites/default/files/resources/United-States-Government-Policy-for-Oversight-of-DURC-FINAL-version-032812-1.pdf. Accessed 6 October 2015.
13. Patterson AP, Tabak LA, Fauci AS, Collins FS, Howard S. Research funding. A framework for decisions about research with HPAI H5N1 viruses. Science 2013; 339:1036-7.
14. Fouchier RAM, Kawaoka Y, Cardona C, et al. Avian flu: gain-of-function experiments on H7N9. Nature 2013; 500:150-1.
15. Fouchier RAM, Kawaoka Y, Cardona C, et al. Gain-of-function experiments on H7N9. Science 2013; 341:612-3.
16. Wain-Hobson S. An avian H7N1 gain-of-function experiment of great concern. MBio 2014; 5.
17. Rey F, Schwartz O, Wain-Hobson S. Gain-of-function research: unknown risks. Science 2013; 342:311.
18. Mahmoud A. Gain-of-function research: unproven technique. Science 2013; 342:310-1.
19. Board on Life Sciences; Division on Earth and Life Studies; Committee on Science, Technology and Law; Policy and Global Affairs; Board on Health Sciences Policy; National Research Council; Institute of Medicine. Potential risks and benefits of gain-of-function research: summary of a workshop. Washington, DC: National Academies Press, 2015. http://www.ncbi.nlm.nih.gov/pubmed/25719185. Accessed 23 April 2015.
20. Greenfieldboyce N. NIH allows restart of MERS research that had been questioned. NPR, 18 December 2014. http://www.npr.org/sections/health-shots/2014/12/18/371686933/nih-allows-restart-of-mers-research-that-was-deemedtoo-risky. Accessed 6 October 2015.
21. Enserink M. Dutch appeals court dodges decision on hotly debated H5N1 papers. Science. 16 July 2015, Updated 17 July 2015. http://news.sciencemag.org/europe/2015/07/dutch-appeals-court-dodges-decision-hotly-debated-h5n1-papers. Accessed 21 July 2015.
22. National Science Advisory Board for Biosecurity. Framework for conducting risk and benefit assessments of gain-of-function research, 2015. http://osp.od. nih.gov/sites/default/files/resources/NSABB-Framework-for-Risk-and-Benefit-Assessments-of-GOF-Research-APPROVED.pdf. Accessed 6 October 2015.
23. Klotz LC, Sylvester EJ. the consequences of a lab escape of a potential pandemic pathogen. Front Public Health 2014; 2:116.
24. Russell CA, Kasson PM, Donis RO, et al. Improving pandemic influenza risk assessment. Elife 2014; 3:e03883.
25. Lipsitch M, Plotkin JB, Simonsen L, Bloom B. Evolution, safety, and highly pathogenic influenza viruses. Science 2012; 336:1529-31.
26. Lipsitch M, Galvani AP. Ethical alternatives to experiments with novel potential pandemic pathogens. PLoS Med 2014; 11:e1001646.
27. Safronetz D, Geisbert TW, Feldmann H. Animal models for highly pathogenic emerging viruses. Curr Opin Virol 2013; 3:205-9.
28. Roberts A, Deming D, Paddock CD, et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog 2007; 3:e5.
29. Kilianski A, Baker SC. Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors. Antiviral Res 2014; 101:105-12.
30. Zhao J, Li K, Wohlford-Lenane C, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A 2014.
31. Agrawal AS, Garron T, Tao X, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 2015; 89:3659-70.
32. Griffin DE, Pan CH. Measles: old vaccines, new vaccines. Curr Top Microbiol Immunol 2009; 330:191-212.
33. Graham RL, Becker MM, Eckerle LD, Bolles M, Denison MR, Baric RS. A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med 2012; 18:1820-6.
34. Smith EC, Case JB, Blanc H, et al. Mutations in coronavirus nonstructural protein 10 decrease virus replication fidelity. J Virol 2015.
35. Coffey LL, Beeharry Y, Bordería AV, Blanc H, Vignuzzi M. Arbovirus high fidelity variant loses fitness in mosquitoes and mice. Proc Natl Acad Sci U S A 2011; 108:16038-43.
36. Rozen-Gagnon K, Stapleford KA, Mongelli V, et al. Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models. PLoS Pathog 2014; 10:e1003877.
37. Xie X, Wang H, Zeng J, et al. Foot-and-mouth disease virus low-fidelity polymerase mutants are attenuated. Arch Virol 2014; 159:2641-50.
38. Baek YH, Song M-S, Lee E-Y, et al. Profiling and characterization of influenza virus N1 strains potentially resistant to multiple neuraminidase inhibitors. J Virol 2015; 89:287-99.
39. Marjuki H, Mishin VP, Chesnokov AP, et al. Neuraminidase mutations conferring resistance to oseltamivir in influenza A(H7N9) viruses. J Virol 2015; 89:5419-26.
40. Wand ME, Bock LJ, Bonney LC, Sutton JM. Retention of virulence following adaptation to colistin in Acinetobacter baumannii reflects the mechanism of resistance. J Antimicrob Chemother 2015.
41. de Jong YP, Dorner M, Mommersteeg MC, et al. Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Sci Transl Med 2014; 6:254ra129.
42. Keck Z, Angus AGN,WangW, et al. Non-random escape pathways froma broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412-423. PLoS Pathog 2014; 10:e1004297.
43. Caskey M, Klein F, Lorenzi JCC, et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 2015.
44. Audet J,WongG,WangH, et al.Molecularcharacterizationof themonoclonal antibodies composing ZMAb: A protective cocktail against Ebola virus. Sci Rep 2014; 4:6881.
45. Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014; 514:47-53.
46. Hanna A, Banks J, Marston DA, Ellis RJ, Brookes SM, Brown IH. Genetic characterization of highly pathogenic avian influenza (H5N8) virus from domestic ducks, England, November 2014. Emerg Infect Dis 2015; 21:879-82.
47. Koel BF, van der Vliet S, Burke DF, et al. Antigenic variation of clade 2.1 H5N1 virus is determined by a few amino acid substitutions immediately adjacent to the receptor binding site. MBio 2014; 5:e01070-14.
48. Koel BF, Mögling R, Chutinimitkul S, et al. Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses. J Virol 2015; 89:3763-75.
49. Davis CT, Chen L-M, Pappas C, et al. Use of highly pathogenic avian influenza A(H5N1) gain-of-function studies for molecular-based surveillance and pandemic preparedness. MBio 2014; 5.
50. Schultz-Cherry S, Webby RJ, Webster RG, et al. Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness. MBio 2014; 5.