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Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to Infection

Sakala, Isaac; Chaudhri, Geeta; Buller, R Mark; Nuara, Anthony A.; Bai, Hongdong; Chen, Nanhai; Karupiah, Gunasegaran

Description

Ectromelia virus (ECTV), a natural mouse pathogen and the causative agent of mousepox, is closely related to variola virus (VARV), which causes smallpox in humans. Mousepox is an excellent surrogate small-animal model for smallpox. Both ECTV and VARV encode a multitude of host response modifiers that target components of the immune system and that are thought to contribute to the high mortality rates associated with infection. Like VARV, ECTV encodes a protein homologous to the ectodomain of...[Show more]

dc.contributor.authorSakala, Isaac
dc.contributor.authorChaudhri, Geeta
dc.contributor.authorBuller, R Mark
dc.contributor.authorNuara, Anthony A.
dc.contributor.authorBai, Hongdong
dc.contributor.authorChen, Nanhai
dc.contributor.authorKarupiah, Gunasegaran
dc.date.accessioned2015-12-07T22:44:44Z
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/1885/25318
dc.description.abstractEctromelia virus (ECTV), a natural mouse pathogen and the causative agent of mousepox, is closely related to variola virus (VARV), which causes smallpox in humans. Mousepox is an excellent surrogate small-animal model for smallpox. Both ECTV and VARV encode a multitude of host response modifiers that target components of the immune system and that are thought to contribute to the high mortality rates associated with infection. Like VARV, ECTV encodes a protein homologous to the ectodomain of the host gamma interferon (IFN-γ) receptor 1. We generated an IFN-γ binding protein (IFN-γbp) deletion mutant of ECTV to study the role of viral IFN-γbp (vIFN-γbp) in host-virus interaction and also to elucidate the contribution of this molecule to the outcome of infection. Our data show that the absence of vIFN-γbp does not affect virus replication per se but does have a profound effect on virus replication and pathogenesis in mice. BALB/c mice, which are normally susceptible to infection with ECTV, were able to control replication of the mutant virus and survive infection. Absence of vIFN-γbp from ECTV allowed the generation of an elective host immune response that was otherwise diminished by this viral protein. Mice infected with a vIFN-γbp deletion mutant virus, designated ECTV-IFN-γbpΔ, produced increased levels of IFN-γ and generated robust cell-mediated and antibody responses. Using several strains of mice that exhibit differential degrees of resistance to mousepox, we show that recovery or death from ECTV infection is determined by a balance between the host's ability to produce IFN-γ and the virus' ability to dampen its effects.
dc.publisherAmerican Society for Microbiology
dc.sourceJournal of Virology
dc.subjectKeywords: binding protein; gamma interferon; gamma interferon binding protein; gamma interferon receptor; unclassified drug; virus protein; animal cell; animal experiment; animal model; antibody response; article; controlled study; Ectromelia virus; female; gene de
dc.titlePoxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to Infection
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume81
dc.date.issued2007
local.identifier.absfor110704 - Cellular Immunology
local.identifier.ariespublicationu6800332xPUB37
local.type.statusPublished Version
local.contributor.affiliationSakala, Isaac, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChaudhri, Geeta, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBuller, R Mark, Saint Louis University Health Sciences Center
local.contributor.affiliationNuara, Anthony A., Saint Louis University Health Sciences Center
local.contributor.affiliationBai, Hongdong, Saint Louis University Health Sciences Center
local.contributor.affiliationChen, Nanhai, Saint Louis University Health Sciences Center
local.contributor.affiliationKarupiah, Gunasegaran, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue7 (April)
local.bibliographicCitation.startpage3346
local.bibliographicCitation.lastpage3353
local.identifier.doi10.1128/JVI.01927-06
dc.date.updated2015-12-07T11:28:05Z
local.identifier.scopusID2-s2.0-33947376438
CollectionsANU Research Publications

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