Potential Risks and Benefits of Gain-of-Function Research Summary of a Workshop (2015) / Chapter Skim
Currently Skimming:
3 Gain-of-Function Research: Background and Alternatives
3 Gain-of-Function Research: Background and Alternatives
Pages 21-28
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 21... ...
gave an overview of the current scientific and technical approaches to the research on pandemic strains of influenza and Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)
|
From page 22... ...
For instance, researchers now have advanced molecular technologies, such as reverse genetics, which allow them to produce de novo recombinant viruses from BOX 3-1 General Virology Questions and Questions Specific to Influenza, SARS, and MERS Research • Why/how does the virus infect and kill mammals? o hat are the critical host range and virulence determinants of W MERS-CoV?
|
From page 23... ...
Like Subbarao and Kawaoka, Baric listed experiments important for the identification of determinants of pathogenesis and virulence, defined the virus-host interaction networks, and described the alleles responsible for susceptibility and the host response patterns that drive a pathogenic or protective responses. However, he specifically noted that transmissibility studies for SARS and MERS-CoV actually fall in a different category than influenza research because of fundamental biological differences between these viruses.
|
From page 24... ...
Molecular methods help with the characterization of antigenic variants, elucidate the biological basis for adverse outcomes associated with vaccine candidates, and determine the basis for attenuation and stability of vaccine candidates. Subbarao also explained that one of the important applications of GoF research is the development of animal models, especially in the case of pathogens with pandemic potential, because to get approval to study a countermeasure compound in humans, the Food and Drug Administration's animal rule requires the presence of disease that mimics the human disease in an animal model.
|
From page 25... ...
David Relman, Stanford University, and the panelists of Session 2 expressed the view that GoF experiments generating viruses with increased virulence, transmissibility, and pathogenicity would clearly define the line that would prompt the use of alternatives. Imperiale explained that, with respect to the GoF terminology, whenever researchers are working with RNA viruses, GoF mutations are naturally arising all the time and escape mutants isolated in the laboratory appear "every time someone is infected with influenza." He also commented that the term GoF was understood a certain way by attendees of this symposium, but when the public hears this term "they can't make that sort of nuanced distinction that we can make here" so the terminology should be revisited.
|
From page 26... ...
• Adaptation of MERS-CoV to animal models • lucidating the molecular determinants of transmissibility by the airborne E route (influenza) • lucidating the biological basis for adverse outcomes associated with can E didate SARS vaccines • Conclusive experiments to demonstrate the biological significance of o novel gene products o genetic differences between isolates from animals and/or humans for newly emerged viruses, e.g., H7N9, H5N8, H5N2, H10N7, and H10N8 influenza and MERS-CoV o Virulence determinants of newly emerged viruses, e.g., H7N9, H5N8, H5N2, H10N7, and H10N8 influenza and MERS-CoV • Molecular basis for resistance to antiviral drugs and MAbs • Viral evolution under immune pressure • Viral evolution in the presence of antiviral drugs SOURCE: Subbarao's ideas on when she believes virological research crosses the line into GoF as defined by the U.S.
|
From page 27... ...
In addition, although working with low pathogenic avian influenza viruses provides a safer approach, Kawaoka explained that "highly pathogenic avian influenza differ from low pathogenic viruses in their kinetics of virus replication and tropism" and therefore the data can be misleading. Other alternatives discussed by Kawaoka and Dr.
|
From page 28... ...
Its engineered influenza A strain, which contained this specific microRNA target site, did not prevent influenza replication and transmissibility in ferrets, but it did attenuate influenza pathogenicity in mice and presumably in humans. Imperiale and later Kawaoka agreed that it constitutes a promising approach.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.