ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Hoi Tong Wong is first author on ‘ Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism’, published in JCS. Hoi Tong is a PhD student in the lab of Dr Daniel Salamango at Stony Brook University, New York, investigating host–pathogen interactions at the molecular level.
Hoi Tong Wong
How would you explain the main findings of your paper in lay terms?
When we encounter a viral pathogen like SARS-CoV-2, our innate immune system is activated, and different chemicals and proteins are released to target the foreign invader. Interferons are one of the signaling proteins released, and they are important for cell communication and activation of other anti-viral defenses. However, SARS-CoV-2 has developed countermeasures that suppress our innate immune response. One of the ways the virus does this is by expressing an accessory protein called ORF6, which has been shown to be a potent interferon suppressor. ORF6 accumulates at multiple membrane compartments, including the nuclear envelope, where it can bind to nuclear import complexes to block protein translocation into the nucleus; therefore, interferon production is inhibited, and our innate immune response is suppressed. The relationship between ORF6 localization and interferon antagonism has not been well classified. In our study, we used genetic, pharmacological and biochemical techniques to show that ORF6 localization is independent of its ability to block interferon production and suppression of the innate immune response. This alludes to other possible ORF6 functions that are yet to be explored.
Were there any specific challenges associated with this project? If so, how did you overcome them?
In general, I find working with different drugs and inhibitors tricky, because you have to optimize the timing and concentrations of your treatments. One challenge I faced was testing the STAT1 response to interferon treatment in A549 cells. After treating cells with interferon, they are prepared for immunofluorescence, but it's hard to know whether the drug treatment worked until the very end of the experiment (when we image our cells). We performed multiple iterations of this experiment until we found the optimal conditions. We also had a similar experience with our brefeldin A and digitonin experiments, but with perseverance and a little creativity, they were a success!
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
I would have to say it was when I saw ORF6 relocalizing to the Golgi after brefeldin A treatment in real time. I thought it was amazing to see the Golgi reassemble itself after being disrupted and to watch ORF6 colocalizing with it. This moment reaffirmed our hypothesis that ORF6 is most likely a peripheral membrane protein.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science encapsulates a wide audience and is comprehensive of many different topics. We wanted our story to reach people beyond the field of virology and thought this journal was a perfect fit.
ORF6 localization, and disruption of importin-α and STAT1. The images show (left) mCherry-tagged ORF6 localized at the Golgi, (middle) mCherry-untagged ORF6 inhibiting translocation of transcription factor STAT1 after interferon stimulation, and (right) mCherry-untagged ORF6 mutant disrupting localization of the nuclear import protein importin-α (right).
ORF6 localization, and disruption of importin-α and STAT1. The images show (left) mCherry-tagged ORF6 localized at the Golgi, (middle) mCherry-untagged ORF6 inhibiting translocation of transcription factor STAT1 after interferon stimulation, and (right) mCherry-untagged ORF6 mutant disrupting localization of the nuclear import protein importin-α (right).
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I have been fortunate enough to join the Salamango lab and to be under the guidance of Dr Daniel Salamango. He continues to challenge and push me to be a critical thinker and a better scientist. I also appreciate the time he takes out of his busy day to give me advice and explain confusing concepts to me.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I have always been a curious person and enjoyed learning about living things surrounding us. I think a lot of my defining moments came from my high school biology lab, where I found it fascinating to see the concepts we learned in the classroom be applied in front of me.
Who are your role models in science? Why?
I would say my undergraduate PI, Dr Regina Lamendella, because she played a big role in my decision to pursue a career in science. As an undergraduate student, I was unsure of what I wanted to do and didn't even know what research was. But after joining her lab, I gained many invaluable experiences and learned a lot under her mentorship. She is an inspirational scientist who doesn't let any obstacles stop her from achieving her goals.
What's next for you?
Currently, I'm not entirely sure what I want to do after graduation, but I hope to stay in the field of virology and continue making contributions to the field.
Tell us something interesting about yourself that wouldn't be on your CV
Outside of the lab, I enjoy traveling and exploring new places.
Hoi Tong Wong's contact details: Stony Brook University, Stony Brook, New York, NY 11794, USA.
E-mail: [email protected]
