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- Andersson, I., et al.
(författare)
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Human MxA Protein Inhibits the Replication of Crimean-Congo Hemorrhagic Fever Virus
- 2004
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 78:8, s. 4323-4329
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Tidskriftsartikel (refereegranskat)abstract
- Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Nairovirus within the family Bunyaviridae and is the causative agent of severe hemorrhagic fever. Despite increasing knowledge about hemorrhagic fever viruses, the factors determining their pathogenicity are still poorly understood. The interferon-induced MxA protein has been shown to have an inhibitory effect on several members of the Bunyaviridae family, but the effect of MxA against CCHFV has not previously been studied. Here, we report that human MxA has antiviral activity against CCHFV. The yield of progeny virus in cells constitutively expressing MxA was reduced up to 1,000-fold compared with control cells, and accumulation of viral genomes was blocked. Confocal microscopy revealed that MxA colocalizes with the nucleocapsid protein (NP) of CCHFV in the perinuclear regions of infected cells. Furthermore, we found that MxA interacted with NP by using a coimmunoprecipitation assay. We also found that an amino acid substitution (E645R) within the C-terminal domain of MxA resulted in a loss of MxA antiviral activity and, concomitantly, in the capacity to interact with CCHFV NP. These results suggest that MxA, by interacting with a component of the nucleocapsid, prevents replication of CCHFV viral RNA and thereby inhibits the production of new infectious virus particles.
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- Mirazimi, A, et al.
(författare)
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Free thiol groups are essential for infectivity of human cytomegalovirus
- 1999
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 8080 ( Pt 11), s. 2861-2865
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Tidskriftsartikel (refereegranskat)abstract
- The membrane-impermeable thiol blocker 5′5-dithiobis 2- nitrobenzoic acid (DTNB) blocked infectivity of human cytomegalovirus (CMV) although the virus still bound to cells. DTNB-treated CMV regained 65% of its infectivity after incubation with the disulfide bond-reducing agent dithiothreitol. These observations suggest that free thiol groups on CMV are required for infectivity and may participate in disulfide bond formation during virus entry.
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- Sjolin, H, et al.
(författare)
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Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection
- 2002
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 195:7, s. 825-834
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are major contributors to early defense against infections. Their effector functions are controlled by a balance between activating and inhibiting signals. To date, however, the involvement of NK cell activating receptors and signaling pathways in the defense against pathogens has not been extensively investigated. In mice, several NK cell activating receptors are coexpressed with and function through the immunoreceptor tyrosine-based activation motif (ITAM)-bearing molecule KARAP/DAP12. Here, we have analyzed the role of KARAP/DAP12 in the early antiviral response to murine cytomegalovirus (MCMV). In KARAP/DAP12 mutant mice bearing a nonfunctional ITAM, we found a considerable increase in viral titers in the spleen (30–40-fold) and in the liver (2–5-fold). These effects were attributed to NK cells. The formation of hepatic inflammatory foci appeared similar in wild-type and mutant mice, but the latter more frequently developed severe hepatitis with large areas of focal necrosis. Moreover, the percentage of hepatic NK cells producing interferon γ was reduced by 56 ± 22% in the absence of a functional KARAP/DAP12. This is the first study that shows a crucial role for a particular activating signaling pathway, in this case the one induced through KARAP/DAP12, in the NK cell–mediated resistance to an infection. Our results are discussed in relation to recent reports demonstrating that innate resistance to MCMV requires the presence of NK cells expressing the KARAP/DAP12-associated receptor Ly49H.
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