Abstract
Type I interferons (IFN) have been shown to play an important role for inhibiting Dengue virus (DENV) infection. Identifying IFN-induced cellular proteins are essential for understanding its mechanisms against DENV. Here we established stable Huh7-derived cell lines expressing the IFN-induced cell membrane protein BST2 (Huh7-BST2) or its variant bearing a V5 tag at the C-terminal (Huh7-BST5CV5). These cell lines were infected with DENV to determine proteins modulating their anti-DENV response. We found that expression of BST2 did not affect the efficiency of DENV infection and intracellular replication. Rather, it significantly reduced the virion yield of the infected cells, particularly at low MOI infection. In addition, BST2 also decreased the foci formation and the size of infectious foci in cultured Huh7 monolayers with media containing methocellulose. The addition of the V5 tag at C-terminal inhibited the GPI modification of BST2 and blocked its shift from endoplasm to cytoplastic membrane. BST2CV5 did not affect DENV infection and foci formation in Huh7 cells but reduced virion yield by 1 log at low MOI infection. Interestingly, intracellular BST2CV5 expression was reduced by high level of DENV production.ConclusionOur results imply that BST2 is a functional mediator of the IFN response against DENV infection. BST2 inhibits the release of DENV virions from Huh7 cells and limits viral cell-to-cell transmission. BST2CV5 variant is unable to inhibit DENV release but impairs viral infection in cells.
Highlights
Dengue virus (DENV) belongs to the family Flaviviridae, and DENV infection remains a global public health problem due to a lack of effective treatment or vaccine [1,2,3]
Our results imply that BST2 is a functional mediator of the IFN response against DENV infection
BST2 inhibits the release of DENV virions from Huh7 cells and limits viral cell-to-cell transmission
Summary
Dengue virus (DENV) belongs to the family Flaviviridae, and DENV infection remains a global public health problem due to a lack of effective treatment or vaccine [1,2,3]. Most infected patients experience dengue fever, but 2 to 20% of all cases manifest as dengue hemorrhagic fever, a severe and often lethal illness [5]. Mice with deficiencies in the type I IFNs production or JAK-STAT signaling pathway are susceptible to DENV infection [9,10,11]. Low levels of the IFN-a/b producing plasmacytoid dendritic cells have been observed in dengue hemorrhagic fever patients [12,13]. Secretion of type I interferon by dendritic cells and mast cells contributes to the generation of antiviral innate and adaptive immune responses [14,15,16]
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