Beauty of viral strategies and beauty industry

You'd never think there is a link between algal blooms, viruses, and anti-aging cosmetics, but apparently, there is. It lies behind quite a remarkable host-virus interaction and quite a complex but fascinating science underpinning it.

Emiliania huxleyi known as dominant bloom-forming algae has its specific EhV-86 virus that has a significant role in regulating those blooms. The complete genome of EhV-86 coccolithovirus was sequenced back in 2005 by Wilson et al. The study revealed the presence of genes coding for sphingolipids production. Interestingly and uniquely for algal viruses, the presence of RNA polymerases that are being expressed during the infection was revealed, implying viral ability to encode the transcription machinery within the host. The fact that lipids produced by EhV-86 are homologs to the ones produced by E. huxleyi, makes this quite a remarkable finding. It means that there is an exciting pathway for sphingolipids production within the host and there is another quite similar but not entirely similar within the virus that gets incorporated into the host's one during the infection.

Sphingolipids coding genes have not been seen in viral genome before the mentioned study, they are known to be present in membranes of eukaryotes and some prokaryotes. Synthesis of sphingolipids leads to the ceramide synthesis which is responsible for growth suppression and programmed cell death signaling.

A recent work done by Ziv et al. (2016) looked closer at the sphingolipids production pathway, lipid structure, and function. Authors took various approaches to access those questions.

Briefly, the described biosynthetic pathway starts with the expression of some virus-encoded enzymes (SPT) that are involved in the viral sphingolipids biosynthetic pathway. That induces a shift in the substrate preference that leads to the production of particular viral sphingolipid bases that are different from those produced in healthy cells. The production of glycosphingolipids vital for viral assembly happens further.

The coexpression of host and viral genes responsible for SPT enzyme was assessed by qPCR and showed that viral SPT genes were upregulated when the host’s downregulated from the beginning of the infection.
Western blot and MS analysis revealed viral proteins increase during the course of infection, therefore confirming, that the modulation of the host’s pathway is happening both at the RNA and protein levels.
Authors also examined the SPT enzyme substrate preference. Unlike infected cells, SPT of healthy cells did not change the preference for the substrate that has been seen in viral enzymes.
By inhibiting the sphingolipids formation with myriocin, authors confirmed the importance of SPT for the viral replication and concluded that the infection is dependent on the SPT activity to produce sphingoid bases (structural component of sphingolipids). LC-MS analysis showed a clear shift towards the production of hydrolyzed bases after the infection.

Interestingly, there was a missing link in the viral pathway: it was lacking the enzyme reductase. Authors suggested that one of the strategies virus can use to deal with it is to use the auxiliary metabolic genes and increase specific host’s metabolic capabilities. The transcriptomics data confirmed that suggestion showing the upregulation of the host reductase gene.

This work also provides a comprehensive analysis of the possible role of sphingolipids in the viral life cycle. As viral bases are more hydrophobic, they are more likely to suppress biophysical properties. The fact that viral bases are hydroxylated means that the membrane becomes less permeable and more resistant to environmental stresses.

This study provides an insight into the interaction between E. huxleyi and EhV-86. Giving the fact that E. huxleyi is one of the most abundant bloom-forming algae and viral infection is one of the major ways of regulating them, this study gives an important addition to the existing knowledge with possible implications for further research on food webs and biogeochemical cycles.
Another interesting view of this work is the evolutionary approach: together with the previous research, it makes the reader consider the horizontal gene transfer and coevolution between the host and its virus. Work on the evolutionary view of this interaction has been done by Monier et al. (2009).

Authors of the paper focus on the ecological role of the findings, however, there is another interesting route which is a biotechnological application. Sphingolipids are used in the anti-aging cosmetics production and usually being extracted from mammalian cells or algae (Takekoshi et al. 2002). This study presents a machinery that produces the industrially targeted compound and therefore opens a field for further biotechnological research. Next steps would be to look at the comparability of the lipids produced by viruses to the ones used in the cosmetic industry and look for the ways of scaling up that machinery.

The paper was of a particular interest to me as both metabolic pathways and algae viruses interactions are the topics I’d like to explore. Methods and results are quite complicated, however, with a very detailed document with supplement information, this work gives a very in-depth experiment design and, in my opinion, is a great example of precise molecular work.

Paper reviewed:

Ziv, C., Malitsky, S., Othman, A., Ben-Dor, S., Wei, Y., Zheng, S., Aharoni, A., Hornemann, T. and Vardi, A. (2016). Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga. Proceedings of the National Academy of Sciences, 113(13), pp.E1907-E1916.

Further reading:

Monier, A., Pagarete, A., de Vargas, C., Allen, M., Read, B., Claverie, J. and Ogata, H. (2009). Horizontal gene transfer of an entire metabolic pathway between a eukaryotic alga and its DNA virus. Genome Research, 19(8), pp.1441-1449.

Allen, M., Forster, T., Schroeder, D., Hall, M., Roy, D., Ghazal, P. and Wilson, W. (2006). Locus-Specific Gene Expression Pattern Suggests a Unique Propagation Strategy for a Giant Algal Virus. Journal of Virology, 80(15), pp.7699-7705.

Wilson, W. H., et al. (2005). "Complete Genome Sequence and Lytic Phase Transcription Profile of a Coccolithovirus." Science 309(5737): 1090-1092.