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2004;78:8312C8321. isolated in the 1940s, whereas both West African and Asian strains were discovered in the 1960s. Identification and diagnosis of ZIKV has been and continues to be confounded by its overlap in geographic range, vector space, symptomology and serological cross-reactivity with other flaviviruses such as dengue computer virus (DENV) (Ioos et al., 2014; Zammarchi et al., 2015). A large body of literature has provided evidence for a potential dual role for CD8+ T cells in protection and pathogenesis during DENV contamination (Screaton et al., 2015; Tang et al., 2015; Weiskopf and Sette, 2014; Zellweger and Shresta, 2014). Epidemiologic studies indicate that Severe Dengue is most often seen in individuals experiencing a heterotypic DENV infection after prior seroconversion to at least one of the other three serotypes (Guzman et al., 2000; Sangkawibha et al., 1984). Some studies showed cross-reactive CD8 T cells are more activated during secondary infection (Mongkolsapaya et al., 2003) with a suboptimal T cell phenotype (Mongkolsapaya et al., 2006) (Imrie et al., 2007; Mangada and Rothman, 2005) suggesting a possible pathogenic role for cross-reactive T cells. However, recently emerging literature points to a protective role for T cells in DENV infection (Weiskopf et al., 2013; Weiskopf et al., 2015), and our previous work on DENV using mouse models (Prestwood et al., 2012b; Yauch et al., 2010; Yauch et al., 2009; Zellweger et al., 2014; Zellweger et al., 2013; Zellweger et al., 2015) in C57BL/6 and 129/Sv mice lacking type I IFN receptor (IFNAR) alone or both type Cannabichromene I and II IFN receptors (AB6, A129, and AG129) has provided multiple lines of evidence indicating a protective role for CD8+ T cells. H-2b mouse models of ZIKV infection recently have been established in WT C57BL/6 mice treated with blocking anti-IFNAR monoclonal antibody and in gene-deficient mice that globally lack IFNAR or both IFNAR and type II IFN receptors (Dowall et al., 2016; Govero et al., 2016; Lazear et al., 2016; Rossi et al., 2016). To investigate IFN receptor-competent CD8+ T cell responses in H-2b mice, in the present study we established a model of ZIKV infection in LysMCre+IFNARfl/fl C57BL/6 mice, which lack IFNAR in a subset of myeloid cells but express normal IFNAR levels on T cells, B cells, and most dendritic cells (Clausen et al., 1999; Diamond et al., 2011). We infected both LysMCre+IFNARfl/fl C7BL/6 mice and anti-IFNAR antibody-treated wild-type (WT) C57BL/6 mice with ZIKV MR766 and FSS13025 strains and mapped the H-2b-restricted CD8+ T cell responses. Additionally, we demonstrated a protective role for CD8+ T cells in controlling ZIKV infection in LysMCre+IFNARfl/fl mice. Our work provides an immunocompetent LATS1 and well-characterized H-2b mouse model for investigating protective gene deletion is efficient in Cannabichromene mature macrophages (83C98%) and granulocytes (100%) but partial for CD11C+ splenic dendritic cells (16%) (Clausen et al., 1999; Diamond et al., 2011). LysMCre+IFNARfl/fl and WT C57BL/6 mice were infected intravenously with MR766 or FSS13025, and levels of infectious virus in serum, liver, spleen, and brain at 1 and 3 Cannabichromene days after infection were determined. At day 1 post-infection, the infectious virus was detectable in all of the tissues tested in LysMCre+IFNARfl/fl mice infected with MR766 (Figure 2A) and FSS13025 (Figure 2B), whereas virus was undetectable in WT mice. At day Cannabichromene 3 post-infection, infectious ZIKV were still detectable in tissues of LysMCre+IFNARfl/fl mice. Based on these results, LysMCre+IFNAR1fl/fl mice, unlike WT mice, are susceptible to ZIKV infection. Open in a separate.