Sunday, September 25, 2016

First Discovery of "Multicomponent" Animal Virus

In a recent article in the journal Cell Host & Microbe, scientists have discovered the first clear evidence of a multicomponent virus that can infect animal cells. Ranging back into the 1970’s, examples of multicomponent viruses, those that have their genome separated into multiple distinct segments, have been found commonly within both plants and fungi.1 Typically, most animal viruses package their entire genome into a single virus particle, which alone has the potential to infect cells and replicate itself within them. Multicomponent viruses, however, have numerous unique particles that collectively make up the viral genome, and at least two or more of these different types of particles are required for successful infection and replication within cells. While many scientists believe that this segmentation may allow for the virus to have more control over genome expression and variation, a higher rate of infection is logically required so that all of the various particles may be successfully transmitted into the cell. Presumably, this requirement may be one reason why multicomponent viruses are previously unknown to animals, as compared to more stationary plants and fungi. In this study from the U.S Army Medical Research Institute of Infectious Diseases, two new examples of multicomponent pathogens were discovered, one named Guaico Culex virus (GCXV), isolated from mosquitoes in Central and South America, and one isolated from red colobus monkeys in Uganda, a variant of the Jingmen Tick virus (JMTV). The discovery of these multicomponent viruses and their ability to infect animals has interesting significance both in human health and in the complex and relatively unknown evolutionary history of viruses.
In order to determine the multicomponent nature of these viruses, the researchers sequenced isolates from the mosquitoes and found five distinct particles for GCXV, although the fifth particle was only identified in some of the samples.

Figure 1: Identification of distinct viral particles for GCXV in infected cells2

Interestingly, when these particles were transfected into cells in various combinations, it was found that only segments one through four were necessary for infection and replication, while segment five was not necessary and did not seem to provide any significant improvement in infectivity.2 This was shown through the use of viral plaque formation, which observes the regions of cell death within a cell culture that are caused by viral infection. Whereas in a non-segmented virus, plaques can be formed in the presence of just a single particle, in multicomponent viruses, all of the necessary particles are required in order for these plaques to form. For the JMTV isolates, four distinct segments were found, and were present in all of the samples isolated from both the red colobus monkey and from ticks.2 Ultimately, the sequencing and transfecting of these segments supports the multicomponent nature of these viruses, with the JMTV variant remarkably representing the first known example of a multicomponent virus infecting primates. While the extent of multicomponent animal viruses is yet unknown, the existence of this primate-infecting virus alone suggests that there may be other segmented animal viruses, which may have relevant applications in human and animal health as research expands and develops.
The discovery of these viruses also has significance evolutionarily, as both of these multicomponent viruses, GCXV and the JMTV variant, fit well with a recently classified group of segmented viruses called “jingmenviruses”. Viruses in this category are all segmented into at least four different virus particles, have been found in ticks and other insects across China and South America, and are highly similar (80-90%) to GCXV and the JMTV variant on a genetic level.3 From this information the researchers reasonably suspect that all of the jingmenviruses share a segmented common ancestor. Numerous structural differences among these viruses, however, along with certain genetic differences, suggest incredible diversity within the clade, much of which is yet to be discovered and classified. Another major finding was that GCXV and other jingmenviruses are genetically similar to the unsegmented category of viruses called flaviviruses, although whether the evolutionary pathway diverged from an unsegmented or a segmented common ancestor is yet unknown. While viral evolution is highly complex and unknown to a large extent, the information provided by these newly discovered multicomponent viruses is another important piece in the evolutionary puzzle.

Figure 2: Potential evolutionary relationships and pathways between Jingmenvirus and Flavivirus2

In summary, this study reported the discovery of two new multicomponent viruses, including the first identified example of a virus of this type that can infect animals. Both evolutionarily and health wise, the discovery of these segmented viruses has important implications for future research, as scientists continue to connect together the evolutionary pathways of viruses and work to counter infectious diseases in humans. Ultimately, this study was just the first insight into this new class of viruses, and further examples of animal-infecting multicomponent viruses are needed to determine their prevalence among animals. Based on the isolates extracted from the red colobus monkey, identification of other animal-infecting multicomponent viruses may be found in other monkeys in Africa and South America, especially in places with high numbers of common jingmenvirus vectors like ticks and mosquitoes. Additionally, further examples of these viruses may aid in determining the evolutionary relationship of the Jingmenvirus and Flavivirus clades, particularly through the use of bioinformatics and comparisons of their genomes. Overall, the incredible variation of viruses ranges well beyond our knowledge, and identification of novel classes of viruses such as these are exciting developments in a field with much left to discover.

1 Fulton, W.R. (1980). Biological significance of multicomponent viruses. Annual Review Phytopathology 18, 131-146.

2 Ladner, J.T., Wiley, M.R., Beitzel, B., Kramer, L.D., Tesh, Robert B., Palacios, G., et al. (2016). A multicomponent animal virus isolated from mosquitoes. Cell Host & Microbe 20, 357-367.

3 Shi, M., Lin, X.D., Vasilakis, N., Tian, J.H., Li, C.X., Chen, L.J., Eastwood, G., Diao, X.N., Chen, M.H., Chen, X., et al. (2015). Divergent viruses discovered in arthropods and vertebrates revise the evolutionary history of the Flaviviridae and related viruses. J. Virology 90, 659–669.

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