Bruno Frederico

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Herpesviruses are ubiquitous pathogens that cause much disease. The difficulty of clearing their established infections makes host entry an important target for control. However, while herpesviruses have been studied extensively in vitro, how they cross differentiated mucus-covered epithelia in vivo is unclear. To establish general principles we tracked(More)
Herpesvirus transmission is sporadic, and infection may be asymptomatic or present only with secondary lesions after dissemination. Consequently host entry remains ill-understood. Experimental infections can be informative, but depend on inoculations that are inherently artificial and so need validation. Mice are a widely used experimental host. Alert mice(More)
Gamma-herpesviruses persist in lymphocytes and cause disease by driving their proliferation. Lymphocyte infection is therefore a key pathogenetic event. Murid Herpesvirus-4 (MuHV-4) is a rhadinovirus that like the related Kaposi's Sarcoma-associated Herpesvirus persists in B cells in vivo yet infects them poorly in vitro. Here we used MuHV-4 to understand(More)
The oncogenicity of gamma-herpesviruses (γHVs) motivates efforts to control them and their persistence makes early events key targets for intervention. Human γHVs are often assumed to enter naive hosts orally and infect B cells directly. However, neither assumption is supported by direct evidence, and vaccination with the Epstein-Barr virus (EBV) gp350, to(More)
Dendritic cells (DCs) play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic(More)
Gamma-herpesviruses (γHVs) are widespread oncogenic pathogens that chronically infect circulating lymphocytes. How they subvert the immune check-point function of the spleen to promote persistent infection is not clear. We show that Murid Herpesvirus-4 (MuHV-4) enters the spleen by infecting marginal zone (MZ) macrophages, which provided a conduit to MZ B(More)
Humans with Wiskott-Aldrich syndrome display a progressive immunological disorder associated with compromised Wiskott-Aldrich Syndrome Interacting Protein (WIP) function. Mice deficient in WIP recapitulate such an immunodeficiency that has been attributed to T cell dysfunction; however, any contribution of B cells is as yet undefined. Here we have shown(More)
Lymphocyte proliferation, mobility and longevity make them prime targets for virus infection. Myeloid cells that process and present environmental antigens to lymphocytes are consequently an important line of defence. Subcapsular sinus macrophages (SSMs) filter the afferent lymph and communicate with B-cells. How they interact with B-cell-tropic viruses is(More)
UNLABELLED Lymphocyte colonization by gammaherpesviruses (γHVs) is an important target for cancer prevention. However, how it works is not clear. Epstein-Barr virus drives autonomous B cell proliferation in vitro but in vivo may more subtly exploit the proliferative pathways provided by lymphoid germinal centers (GCs). Murid herpesvirus 4 (MuHV-4), which(More)
Glycoprotein B (gB) is a conserved herpesvirus virion component implicated in membrane fusion. As with many-but not all-herpesviruses, the gB of murid herpesvirus 4 (MuHV-4) is cleaved into disulfide-linked subunits, apparently by furin. Preventing gB cleavage for some herpesviruses causes minor infection deficits in vitro, but what the cleavage contributes(More)