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Poxvirus-encoded gamma interferon binding protein dampens the host immune response to infection

journal contribution
posted on 2023-05-20, 21:00 authored by Sakala, IG, Chaudhri, G, Buller, RM, Nuara, AA, Bai, H, Chen, N, Gunasegaran KarupiahGunasegaran Karupiah
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 the host gamma interferon (IFN-y) receptor 1. We generated an IFN-y binding protein (IFN-ybp) deletion mutant of ECTV to study the role of viral IFN-ybp (vIFN-ybp) 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-ybp 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-ybp from ECTV allowed the generation of an effective host immune response that was otherwise diminished by this viral protein. Mice infected with a vIFN-ybp deletion mutant virus, designated ECTV-IFN-ybp, produced increased levels of IFN-y 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-y and the virus' ability to dampen its effects.

History

Publication title

Journal of Virology

Volume

81

Issue

7

Pagination

3346-3353

ISSN

0022-538X

Department/School

Tasmanian School of Medicine

Publisher

Amer Soc Microbiology

Place of publication

1752 N St Nw, Washington, USA, Dc, 20036-2904

Rights statement

Copyright © 2007, American Society for Microbiology

Repository Status

  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions

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