Ectromelia (Mousepox) Virus



June 9, 2003

The Sanger Institute has sequenced the 208 kb genome of Ectromelia (mousepox) virus in collaboration with Dr. Antonio Alcami of the Department of Pathology, University of Cambridge.

Ectromelia virus (EV) is a member of the poxvirus family. These are complex dsDNA viruses that replicate in the cell cytoplasm and thus encode their own replication and transcription machinery. Members of the poxvirus family include variola virus, one of the most virulent human pathogens that caused smallpox, and vaccinia virus, the smallpox vaccine.

Poxviruses encode a unique collection of genes that evade host immune responses. Some of these viral genes seem to have been acquired from the host and modified during virus evolution to confer an advantage for the virus, and encode homologues of host immune molecules or proteins that target key components of the host defence mechanisms. Some examples are viral proteins that are secreted from infected cells and bind cytokines or chemokines, and intracelular viral proteins that block apoptotic responses or confer resistance to interferon. These findings have increased the interest on poxviruses because further characterisation of these viral immunomodulatory proteins will help us to better understand the function of components of the immune system and to identify novel strategies of immune modulation.

EV is a highly virulent natural pathogen of mice that causes mousepox, a severe disease with high mortality rate that was proposed as a mouse model of human smallpox. EV has been isolated from outbreaks in laboratory mouse colonies and has caused serious disruptions in biomedical research. Mousepox has been used in the past as a model for studies on the pathogenesis of generalised infections, the cellular immune response to viral infections and the genetic determinants of disease susceptibility and resistance. However, EV has been poorly characterised at the molecular level.

We have determined the complete genome sequence of EV Naval.Cam. This virus was derived from the original EV Naval after three rounds of plaque-purification in tissue culture, and was confirmed to retain the high virulence of the parental virus. EV Naval was isolated from an outbreak in 1995 in a laboratory mouse colony at the US Naval Medical Research Institute.

http://www.sanger.ac.uk/Projects/Ectromelia_virus/