Large DNA virus
produces rare sugars

TEM images of Megavirus chilensis in infected Acanthamoeba castellanii cells

Viruses generally are defined as protein-packaged genomes rather than as independent organisms because they are unable to propagate on their own. However, recent studies have shown that some large DNA viruses encode genes for metabolic pathways that make the viruses less dependent on host cell machinery for their propagation. In other words, they carry more genes that support their own survival compared with other viruses. As such, some think these large DNA viruses are evolutionary bridges between nonliving viruses and living organisms.

In a recent Journal of Biological Chemistry paper, researchers reported finding that a nucleocytoplasmic large DNA virus from the Mimiviridae family encodes genes that allow it to produce a rare type of sugar. Nucleocytoplasmic large DNA viruses have large genomes, and some are known to carry genes that encode glycosylation systems, including genes for enzymes and substrates required for the production of complex carbohydrates.

In the JBC study, the authors aimed to identify and characterize the first two enzymes encoded within a Megavirus chilensis gene cluster thought to be involved with a glycosylation pathway. Sequences from two genes in this cluster had been shown to be homologous to bacterial enzymes involved in the production of 2-acetamido-2,6-dideoxy- L-hexoses, which are types of sugars called 6-deoxy-hexosamines. What is striking about these 2-acetamido-2,6-dideoxy-L-hexoses specifically is that they are produced in the L-enantiomer as opposed to the more common D-enantiomer. Although the L-enantiomers of 6-deoxy-hexosamines have been observed on the surfaces of some bacteria, they are otherwise rarely found in nature.

Through a series of sequence, structural and activity analyses, the authors found that the first gene product in the cluster, Mg534, is a 4,6-dehydratase-5-epimerase. The second gene product, Mg535, is a bifunctional 3-epimerase, 4-reductase. Acting sequentially, Mg534 and Mg535 generate the L-enantiomer of the sugar UDP-L-N-acetylrhamnosamine, which is rare in nature like other 6-deoxy-L-hexosamines but confirmed by the authors to be present in M. chilensis viral particles.

No homologues were found in giant viruses from other groups for Mg534 or Mg535 or for Mg536, the next gene product in the cluster that the authors identified as a potential GlcNAc 2-epimerase. However, other large DNA viruses are known to carry genes for rare sugar production, indicating there is a specific and important role for these sugars in the lifecycle of these viruses.

The authors speculate that these sugars could be involved in mediating interactions between viral particles and host cells or perhaps in protecting the virus from cellular components during replication within host cells.

The authors indicate that carrying genes for certain sugars and metabolic pathways makes these viruses less dependent on host cells for these components. In turn, this may allow the viruses to infect a greater range of host cells.

Kelly Hallstrom Kelly Hallstrom (kelly.n.hallstom
@gmail.com) is is a Ph.D. candidate at the University of Massachusetts Medical School.