Saturday, February 26, 2011

Whole-body "Scale" Analysis of a Viral Infection

From the Pasteur Institute in Paris,  Marion Ludwig and collegues report the first whole-body analysis of a viral infection in a vertebrate. Using zebrafish larvae, they were able to observe host-pathogen interactions due to the immediate advantages of being both  small and transparent. Zebrafish have long been a well-established model organism as they are generally small, breed readily, externally fertizable with fast developing embryos, ease of genetic manipulation and high homology with human genes and cell types. As this paper describes, microbiologists are now taking a "pike"-ing to using this fish model .

Researchers experimentally infected the larvae with heat-adapted Infectious Hematopoietic Necrosis Virus (IHNV),  a Rhabdovirus that causes severe disease and hemorrhaging in salmonid fish (trout, salmon, et al.).  They were then able to follow the course and patterns of infection in the entire animal through the use of whole-mount  in situ  hybridization (WISH) and whole-mount immunohistochemistry (WIHC). They found that the primary target of the virus was vascular endothelial cells with the most severe damage in blood vessels. They were able to utilize the virus's temperature sensitivity to examine critical time points of infection. By shifting to the non-permissive temperature at numerous time points post-infection, they determined that if the virus was not inhibited or cleared 12-15 hours post-infection,  pathology would emerge. Unfortunately for the fish, this is too short of a period for the host immune system to respond accordingly.

Though there are dolphinately some set backs to this system (including that there are no known natural viruses of zebrafish) these researchers believe that this can prove to be a valuable tool in the future and most certainly has a plaice in studying viruses. 

- Vy Tran

Ludwig M, Palha N, Torhy C, Briolat V, Colucci-Guyon E, et al. (2011) Whole-Body Analysis of a Viral Infection: Vascular Endothelium is a Primary Target of Infectious Hematopoietic Necrosis Virus in Zebrafish Larvae. PLoS Pathog 7(2): e1001269. doi:10.1371/journal.ppat.1001269

(I'm sorry for all the marine puns. I'm ofishally stopping now.)

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