title: Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.
abstract: Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.
authors.affiliation: Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Olson
authors.affiliation: Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Karem
authors.affiliation: Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Smith
authors.affiliation: Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hughes
authors.affiliation: Poxvirus Team, Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail Stop G-06, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
authors.forename: Inger K
authors.initials: IK
authors.lastname: Damon
mesh_terms: D000818:Animals; D002460:Cell Line; D004196:Disease Outbreaks; D006801:Humans; D051379:Mice; D010641:Phenotype; D010802:Phylogeny; D011817:Rabbits; D012899:Smallpox / Q000453:epidemiology / Q000401:mortality* / Q000821:virology; D015996:Survival Rate; D012901:Variola virus / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification / Q000472:pathogenicity*; D014759:Viral Envelope Proteins / Q000378:metabolism; D010948:Viral Plaque Assay; D014774:Virulence
chemical_list: D014759:Viral Envelope Proteins