Thursday, June 14, 2012

The Universality and Complexity of Viruses: A Brief Story Behind Our New Review

From Bordenstein et al 2006 PLoS Pathogens. Bacteriophage particles are denoted by the arrow heads inside Wolbachia cells that inhabit the testes. Particles are observed to be lysing Wolbachia in the two images on the right, such that DNA is degraded, membranes are detaching from the surface, and particles are exiting the cell.
 100 years ago, we were unaware that viruses even existed. Today, they are recognized as the most abundant biological entity on the planet. Despite their ubiquity, there was an expectation that there would be some form of limit to the distribution of viruses.

In particular, viruses require a host to replicate inside and some host organisms live in such a confined niche that they may be a boundary to the frontier of viruses.

What kinds of hosts are we talking about? Obligate intracellular bacteria or bacteria with reduced genomes that are confined to replication inside host cells. These bacteria comprise some of the most intimate and long-lasting interactions on the planet - Chlamydia, Wolbachia, and the bacterial ancestors of mitochondria and chloroplasts. Are these species unique in that the viral frontier does not reach them? And if it does reach them, do their viruses evolve differently from viruses that live in less constrained niches such as bacteria that replicate in the open environments of land and water.

As it turns out, many obligate intracellular bacteria, especially those that switch hosts, are rampant with mobile genetic elements including viruses.

For a summary of this topic and specific studies on viruses in Wolbachia, my student Jason Metcalf (@JMetcalfVU) and I just published a review in a special issue on viruses in Current Opinion in Microbiology, entitled The complexity of virus systems: the case of endosymbionts

Jason is a M.D./Ph.D. student in the The Vanderbilt Medical Scientist Training Program (MSTP). He joined the lab in the summer of 2011 to develop bacteriophage WO into a therapeutic treatment against its host Wolbachia. The phage could offer a naturally-evolved way to kill Wolbachia involved in human diseases.

A few salient points of the review are:
  1. Wolbachia pipientis infects a vast number of animal species and often has a significant portion of its genome dedicated to proviral sequences of a virus called WO. 
  2. A Wolbachia genome typically has one full temperate virus and several degraded relics of previous WO virus invasions.    
  3. WO biology has updated fundamental theories of viral and endosymbiont evolution, namely The Phage Modular Theory and endosymbiont genome stability. 
  4. Active WO always transfers between Wolbachia coinfections in the same host. 
  5. Despite its rampant mobility, WO exhibits features of genomic constraint related to its intracellular niche, including gene deletions and infrequent acquisition of new genes. 
  6. Active and remnant fragments of WO retain an unusual core genome of head and baseplate genes; other genes are frequently deleted. (would love to know why?)
  7. Up to 87% of the divergent/absent genes between closely related Wolbachia strains is due to prophage WO


  1. From reading on this blog.. Why kill it would seem strategy would be to promote

    Wonder what diseases..

    >>>The phage could offer a naturally-evolved way to kill Wolbachia involved in human diseases.

  2. Hi Doug. Thanks for the questions. Wolbachia is an endosymbiont in arthroods and filarial nematodes. While the Wolbachia are reproductive parasites of arthropods, there are different Wolbachia strains in nematodes that have evolved to become mutualistic with the worms. If Wolbachia is removed from the nematodes, the nematodes are rendered sterile or inviable during larval development. We propose that the phage from arthropod Wolbachia could be utilized to kill Wolbachia in nematodes, thereby treating diseases associated with filarial worms, such as River Blindness, Elephantiasis, and Dog Heartworm.