ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Cecilia Alejandra Vazquez is first author on ‘ Intracellular lipid droplets are exploited by Junín virus in a nucleoprotein-dependent process’, published in JCS. Cecilia Alejandra is a postdoc in the lab of Dr Sandra M. Cordo and Dr Cybele C. García at Universidad de Buenos Aires Int, Buenos Aires, Argentina, where she is interested in all things regarding the ‘One Health’ concept of optimizing the health of people, animals and ecosystems. In particular, I am passionate about host–pathogen interactions, how they can be affected by the environment and how understanding them can lead to the development of new therapies.
Cecilia Alejandra Vazquez
How would you explain the main findings of your paper in lay terms?
In this paper we studied how Junín virus − the causative agent of Argentinean hemorrhagic fever − interacts with its host cell. In particular, we discovered that the content of host cells' lipid droplets is decreased as a direct result of infection. In fact, expression of the viral nucleoprotein alone is enough to partially induce this reduction. We found that the mechanism that leads to this change is lipophagy, selective targeting of lipid droplets for degradation, although the involvement of other mechanisms can't be ruled out. This degradation of lipid droplets then fuels mitochondrial fatty acid β-oxidation, which we found is crucial for the Junín virus life cycle.
Were there any specific challenges associated with this project? If so, how did you overcome them?
We were very interested in visualizing the localization of viral RNA. But, unlike for other viral models, this wasn't that easy for Junín virus. We tested three different anti-dsRNA antibody clones without luck. We thought that maybe the viral nucleoprotein was masking the epitopes on the RNA, so we implemented an antigen retrieval protocol. This didn't work either. Finally, click chemistry had the answer we were looking for, but even then, we had to tweak the protocol in order to co-stain the viral RNA, its nucleoprotein and cellular lipid droplets. I guess the take home message is to not give up and just keep trying new strategies!
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
When this project started, we had evidence that suggested that lipid droplets might be relevant to Junín virus' life cycle, but there were no previous reports that linked this organelle to any member of the Arenaviridae family. So, when I saw that lipid droplet content was reduced in infected cultures in experiment after experiment, I was confident that we were on to something and that this was a phenotype worth studying.
Why did you choose Journal of Cell Science for your paper?
I have a high regard for The Company of Biologists in general and admire the quality of the papers that are published in Journal of Cell Science. Moreover, part of the work in this paper was carried out thanks to The Company of Biologists and Journal of Cell Science Travelling Fellowship, so publishing in this journal was naturally my first choice.
Cell infected with Junín virus. Nascent RNA, shown in green, was labelled using click chemistry; lipid droplet (LDs, cyan) were labelled with LipidTox Deep Red; viral nucleoprotein (NP, red) was immunolabelled using specific antibodies; DAPI-stained nuclei are shown in blue. Scale bar: 10 µm. Inset: detail of NP and viral RNA puncta in apposition to the LD surface (arrows). Regions of interest corresponding to the LD surface are shown in white.
Cell infected with Junín virus. Nascent RNA, shown in green, was labelled using click chemistry; lipid droplet (LDs, cyan) were labelled with LipidTox Deep Red; viral nucleoprotein (NP, red) was immunolabelled using specific antibodies; DAPI-stained nuclei are shown in blue. Scale bar: 10 µm. Inset: detail of NP and viral RNA puncta in apposition to the LD surface (arrows). Regions of interest corresponding to the LD surface are shown in white.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I am lucky to have had great supervisors both as an undergrad and as a graduate student. Thus, I find that who I am as a scientist today has been influenced by all of them: Dr Baez and Dr Jerusalinsky during my first formative years and Dr Cordo and Dr García since the beginning of my PhD until now. The four of them accompanied me in shaping my understanding of what, how, why and for whom I do science.
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?
Before pursuing a career in science, I spent a brief time in medical school. There, I learned about cell biology and molecular biology techniques, and I was smitten. I knew then that my place was not in the hospital but the lab. Years later, my first western blot did not disappoint and seeing those bands on the X-ray film was a dream come true!
What's next for you?
This work was part of my PhD thesis, and I am currently a postdoc in the same lab I completed my PhD in. One of my goals is to continue to explore the fascinating dynamics of lipid droplets and their contents during viral replication. My second objective is to incorporate into this study the effect of the environment, as exposure to substances that can be immune or metabolic modulators can influence host–pathogen interactions.
Tell us something interesting about yourself that wouldn't be on your CV
I love traveling, my dogs and saving images of funny looking cells (e.g. a shamrock-shaped cell in anaphase or a ‘smiling’ cell).
Cecilia Alejandra Vazquez’s contact details: Lab. de Virología (QB20), Dpto. de Química Biológica - Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires Int. Güiraldes 2160, Pabellón 2 - Piso 4° - (C1428EGA) - Ciudad Universitaria, Buenos Aires, República Argentina.
E-mail: [email protected]
