“A virus is a piece of bad news wrapped up in protein” – Sir Peter Medawar, 1983

Viruses have been roaming around this planet for millions of years. They represent the smallest of all self-replicating entities; consisting – in their most basic form – of genetic material protected by a protein shell. Lacking bioenergetic organelles and a protein synthesis machinery, viruses are obligate intracellular parasites that can only replicate within the cells they infect. The ‘life’ cycle of a virus may sound like an easy linear road: a virus finds a cell, finds its way in, makes more copies of itself, and the progeny viruses find their way out of the cell and onto the next cell where the cycle begins all over again. This general concept seen in textbooks, while accurate in principle, assumes that the target cell is a simple passive bystander during these processes. But, what fun would it be to watch an action movie where a burglar breaks in a house and take all s/he wants while the owners of the house…remain silent watching their favorite TV show? Wouldn’t that be a lousy plot? Cells are dynamic units of life and, as such, will respond to stimuli (such as a viral intruder) and do everything they can to maintain homeostasis. I have found that viral infections make a perfect plot for understanding how cells respond to microbes because (almost) every step occurs within the host cell. The combination of cell biology principles with the parasitic nature of viruses provides an ideal biological platform that is both intriguing and beautiful to capture in time.

Confocal micrograph of a primary cardiac culture. Cytoplasm in turquoise, nuclei in magenta; yellow and red staining depicts cardiac fibroblasts and myocytes, respectively. Image by E.E.R.-S.

My research interest focuses on studying study the interplay that occurs between the host cell and the invading virus during different stages of the virus life cycle in both time and space. That is, defining the when, where and how of diverse strategies that viruses employ to create a favorable intracellular environment for their needs and the antiviral responses that cells use to counter-attack the invader. One aspect that virologists often ignore is the fact that the body is composed of a myriad of different cell types; and many viruses have more than a single target cell type within the host. In many cases, these different cell types contribute to distinct necessities of the virus during their transmission cycle. My main research interest is to define antiviral responses that are cell type-specific. Furthermore, I believe that understanding viral evasion strategies that are themselves specific to a cell type highlights the evolutionary pressures that have shaped the dynamics of virus tropism and host range.

Bright-field images of different cell cultures that I have used to study virus-host interactions. Photos by E.E.R-S.

Cardiac cell type-specific antiviral responses

During my Ph.D. training with Dr. Barbara Sherry, I studied how distinct populations of cardiac cells regulate their antiviral responses in a finely-tuned fashion. Many different viruses have the ability to induce cardiac damage, yet cardiac myocytes – the muscle cells responsible for the ‘beating’ of the heart – are non-replenishable. This is because they do not enter the mitotic cycle in adulthood (at least in most species) and, thus, the myocytes in your heart right now are the same ones you had when you were a kid. Yet, here we are. This is largely because cardiac cells – myocytes and fibroblasts in the heart – have evolved many ways to fight against viruses both before a viral infection as well as modulating responses during and after an infection. My work demonstrated the molecular mechanism by which cardiac myocytes pre-arm themselves against viral infections through β-interferon signaling [1] and how cardiac fibroblasts contribute to antiviral responses by amplifying NF-κB-dependent pro-inflammatory responses [2, 3]. My research also showed a novel strategy by which reovirus, a double-stranded RNA virus that replicates in the cytoplasm of the host cells, antagonizes antiviral responses through modulation of the cell mRNA splicing machinery within the nucleus [4].

Expression of reovirus protein µ2 [green] results in redistribution of the splicing factor SRFS2 [red] from nuclear speckles to microtubule-associated filaments within the nucleus [blue]. Image by E.E.R.-S.

Viral entry and egress

As a postdoctoral scientist at UNC-Chapel Hill in Dr. Stanley Lemon‘s lab, I studied (a) how naked and quasi-enveloped hepatitis A virions gain entry into liver cells, (b) how and when these distinct virions release their genetic material into the cytoplasm, and (c) mechanisms of viral egress within extracellular vesicles (EVs) similar to exosomes [5, 6]. During this time, I developed a method to fluorescently and irreversibly label the lipid bilayer that surrounds quasi-enveloped hepatitis A (eHAV) virions to monitor membrane fate and decay during eHAV entry and uncoating. With this tool, I was able to dissect the entry processes that distinct HAV virions engage upon binding to its target cell [7]. This work was funded in part by an NIH T32 fellowship (T32-AI007151).

Tracking the trafficking of quasi-enveloped HAV (eHAV) to monitor quasi-envelope/membrane decay in mammalian lysosomes using confocal microscopy (Rivera-Serrano et al, 2019, eLife)


Vesicle trafficking of hepatitis A virus (green/red) to lysosomes (blue) in hepatocytes (see Rivera-Serrano et al, 2019, eLife). Micrograph by E.E.R.-S.


Flavivirus-cell interactions

Currently, I am a postdoctoral scholar at University of California, Davis studying how different flaviviruses (e.g. Zika, Dengue, HCV) manipulate the host cell during infection for their benefit. My interests lie in defining cellular processes that flaviviruses  hijack to facilitate their replication. Under the guidance of Dr. Ben Montpetit and Dr. Priya Shah, I am using cutting-edge CRISPR-based transcriptional inhibition of host genes important for the replication of these viruses.

Flavivirus life cycle