IFN-Dependent and -Independent Reduction in West Nile Virus Infectivity in Human Dermal Fibroblasts
نویسندگان
چکیده
Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, we demonstrate that neuroinvasive, WNV-New York (WNV-NY), and nonneuroinvasive, WNV-Australia (WNV-AUS60) strains are able to infect and replicate in primary human dermal fibroblasts (HDFs). However, WNV-AUS60 replication and spread within HDFs was reduced compared to that of WNV-NY due to an interferon (IFN)-independent reduction in viral infectivity early in infection. Additionally, replication of both strains was constrained late in infection by an IFN-β-dependent reduction in particle infectivity. Overall, our data indicates that human dermal fibroblasts are capable of supporting WNV replication; however, the low infectivity of particles produced from HDFs late in infection suggests that this cell type likely plays a limited role as a viral reservoir in vivo.
منابع مشابه
Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8+ T Cell Immune Responses against West Nile Virus Infection
Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observe...
متن کاملCell-Specific IRF-3 Responses Protect against West Nile Virus Infection by Interferon-Dependent and -Independent Mechanisms
Interferon regulatory factor (IRF)-3 is a master transcription factor that activates host antiviral defense programs. Although cell culture studies suggest that IRF-3 promotes antiviral control by inducing interferon (IFN)-beta, near normal levels of IFN-alpha and IFN-beta were observed in IRF-3(-/-) mice after infection by several RNA and DNA viruses. Thus, the specific mechanisms by which IRF...
متن کاملDifferential expression of interferon (IFN) regulatory factors and IFN-stimulated genes at early times after West Nile virus infection of mouse embryo fibroblasts.
Although lineage I West Nile virus (WNV) strain Eg101 induced beta interferon (IFN-beta) production as early as 12 h after infection in primary mouse embryo fibroblasts and did not inhibit the JAK-STAT signaling pathway, it was still able to replicate efficiently. To gain insights about possible viral countermeasures used by this virus to suppress the host response, the cell transcriptional pro...
متن کاملPrevalence of West Nile Virus Infection in the Cities of Neka and Shiraz, Iran
Abstract Background and Objective: West Nile virus (WNV) is a member of the genus Flavivirus that can cause viral infections in human. This study aimed at detecting IgG antibodies against WNV in patients of two cities of Neka and Shiraz. Material and Methods: the participants were 46 possible WNV case from Neka (13 women and 10 men) and Shiraz (10 women and 13 men). IgG assay was ...
متن کاملInduction of IFN-β and the Innate Antiviral Response in Myeloid Cells Occurs through an IPS-1-Dependent Signal That Does Not Require IRF-3 and IRF-7
Interferon regulatory factors (IRF)-3 and IRF-7 are master transcriptional factors that regulate type I IFN gene (IFN-alpha/beta) induction and innate immune defenses after virus infection. Prior studies in mice with single deletions of the IRF-3 or IRF-7 genes showed increased vulnerability to West Nile virus (WNV) infection. Whereas mice and cells lacking IRF-7 showed reduced IFN-alpha levels...
متن کامل