Name: Yoshihiro Kawaoka

Affiliation: Professor of Virology, University of Wisconsin-Madison

                  Professor, University of Tokyo

                   Madison, WI, US

                   Tokyo, Japan

 Email: yoshihiro.kawaoka@wisc.edu , kawaoka@ims.u-tokyo.ac.jp

Website:  https://www.vetmed.wisc.edu/people/kawaokay/

                http://www.ims.u-tokyo.ac.jp/imsut/en/lab/microbiologyimmunology/

Could you tell me a bit about what your research entails?

We work on many different aspects of influenza viruses because we are interested in what influenza viruses do in general. We perform surveillance of poultry in the areas in which highly pathogenic avian viruses are enzootic and characterize these viruses to assess their pandemic potential; studies on the molecular mechanism(s) of adaptation of avian influenza viruses to mammals; research on host responses to virus infection with a view to developing antiviral drugs; studies on how new epidemic strains of human influenza viruses emerge; and studies to develop better vaccines. We also generated the 1918 virus and studied its pathogenesis, as well as host responses to this virus in non-human primates.

How did you become interested in influenza research?

I obtained my Master’s and PhD degrees in bacteriology. While I was working towards those degrees, I did participate in influenza virus isolation from birds. But, it wasn’t until I started working as a postdoctoral fellow in Dr. Webster’s lab that I began seriously working on influenza viruses at the molecular level.

In what ways has the 1918 pandemic most influenced your research, and the wider virology and public health field?

After the complete sequencing of the 1918 virus by Jeffery Taubenberger and the synthesis of the virus by Terrence Tumpey and Peter Palese, we also generated this virus and found that it is the only influenza virus that is lethal to nonhuman primates. Yet, we still do not know the molecular basis for this extreme pathogenicity. I realize that I am not answering your question, but, this is still a mystery and something we would like to understand in the near future.

What do you see as the biggest accomplishments/breakthroughs in the field since the 1918 pandemic? Are there any papers that you feel are must reads for those that aren’t familiar with the field (and briefly, why)?

1. Hirst GK (1941). "The agglutination of red blood cells by allantoic fluid of chick embryos infected with influenza virus". Science. 94: 22–23. doi:10.1126/science.94.2427.22

This discovery allowed us to quantify influenza viruses and antibodies to influenza viruses, which, in turn, allowed us to differentiate viruses based on their antigenicity and to quantify immune responses upon infection or vaccination. 

2. A series of papers by Jeffery Taubenberger, who determined the complete sequences of the 1918 virus.

These studies allowed us to generate the 1918 virus, which is the most pathogenic influenza viruses we have ever tested in mammals.

3. Neumann et al. Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9345-50

 This method allows us to generate influenza viruses anyway we want to as long as they are viable, revolutionizing influenza research and making it possible to make vaccines for highly pathogenic viruses such as H5 viruses by attenuating them.

4. Laver, Webster

Studies on the origin of pandemic influenza: III. Evidence implicating duck and equine influenza viruses as possible progenitors of the Hong Kong strain of human influenza

Virology, 51: 383-391, 1973

This was the first paper to suggest that the HA of a human pandemic virus had originated from the HA of non-human viruses. It is interesting to read the transcript of a meeting at that time in which a prominent scientist was questioning this novel concept.   

5. Wilson, Skehel, Wiley

Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution

Nature 289: 366–373, 1981

This paper allowed us to understand the structural basis for the functions of HA, antibody responses, host range, pathogenicity and enabled us to design new vaccine antigens 

What do you see as the main challenges for research in your part of the field in the coming years?

Now that the US NIH has lifted the pause on funding gain-of-function research, we can initiate studies to understand what makes non-human influenza viruses cause pandemics. However, we need to be extremely cautious about how we proceed with such studies so that the NIH does not deem it necessary to impose another moratorium on experiments of dual use research of concern and gain-of-function.