Host-Virus-Dynamics

Our interest in the forces of mortality that act on cells in the ocean led to the development of this research theme. Viruses are known to be abundant in the ocean – but how many are actually infective, who they infect, and the factors that influence infection are all still poorly understood (see our review article with colleagues ranging from trace metal chemists to phage biologists: Zimmerman et al. Nature Reviews Microbiology 2020)! We use several different approaches to try to understand host-virus interactions. The first is culture experiments (Fig. 1) – where we have explored infection kinetics and how they are shaped by the nutrient status of the host cell. Our models here are widespread marine green algae, specifically Bathycoccus, Micromonas (e.g., Bachy et al. EM 2018) and Ostreococcus (Zimmerman et al. EM 2019). In the latter two studies, we tried to understand whether infection changes were connected purely to growth rate or actually shaped by the growth limiting factor. We know that some viruses carry auxiliary metabolic genes – like the cross-domain ones we captured in viruses of bacteria and eukaryotes alike in our earlier metagenomic and targeted metagenomics work (Monier et al. EM 2012). One approach we use is to study responses of both the host and virus at the molecular level using transcriptomics.

In addition to our laboratory studies, we use targeted metagenomics to recover novel viruses directly from the ocean and yet uncultured hosts. We perform single cell sorting at sea to isolate individual cells or populations of algae (e.g. Bathycoccus, Synechococcus) or Choanoflagellates (Fig. 2). This allows us to isolate one part of the microbial community, which we then analyze using different bioinformatic tools to identify its viral pathogens and interactions at microscale rather than recovering metagenomes from bulk water filtrations. For example, using this approach, we were able to characterize a giant virus (875Kb) in the uncultured unicellular predator Bicosta minor expressing a rhodopsin photosystem (Needham et al. PNAS 2019).

Dr. Charles Bachy is leading the cultured host-virus research – he works closely with Prof. Charmaine Yung, who is a faculty member at HKUST as well as Dr. Amy Zimmerman at the University of Chicago, both of whom are former Worden Lab postdocs.

Over the last decade, the fast-evolving field of next-generation sequencing not only exponentially increased the amount of ocean sequencing data publicly available but also lead to the discovery of more and more viruses with a genome size of >300Kb, so called giant viruses (see for example PacVs with a genome size of up to 1605Kb in Needham et al. Philos. Trans. Royal Soc. 2019). Some of these recently discovered eukaryote-infecting marine viruses  approach and  even exceed the genome size of small bacteria. They can encode multiple proteins like tRNAs and elongation factors that have previously been attributed exclusively to cellular lifeforms. Not only are some of their genes challenging our definition of what viruses actually are, but about half of their proteins also have completely unknown functions leaving a lot of room for speculation about what secrets are still to be uncovered.