Interferon (IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-α activity in a dose-dependent manner. This action was reversed by specific monoclonal antibodies to IL-8. The chemokine was able to attenuate the IFN-mediated inhibition of viral replication as determined by measuring infectious virus yield. IL-8 also diminished the ability of IFN to inhibit an early stage of viral replication since IL-8 attenuated the inhibition of the formation of viral proteins. It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated pathway such as early gene expression. The IL-8 inhibitory action on IFN-α antiviral activity was associated with reduced 2′,5′-A oligoadenylate synthetase activity, a pathway well correlative with the anti– encephalomyocarditis virus action of IFN-α. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.
Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood. In this study, we found that herpes simplex virus (HSV) infection induced extensive modification of tankyrase 1 but not tankyrase 2. This modification was dependent on extracellular signal-regulated kinase (ERK) activity triggered by HSV infection. Following HSV-1 infection, tankyrase 1 was recruited to the nucleus. In the early phase of infection, tankyrase 1 colocalized with ICP0 and thereafter localized within the HSV replication compartment, which was blocked in cells infected with the HSV-1 ICP0-null mutant R7910. In the absence of infection, ICP0 interacted with tankyrase 1 and efficiently promoted its nuclear localization. HSV did not replicate efficiently in cells depleted of both tankyrases 1 and 2. Moreover, XAV939, an inhibitor of tankyrase PARP activity, decreased viral titers to 2 to 5% of control values. We concluded that HSV targets tankyrase 1 in an ICP0-and ERK-dependent manner to facilitate its replication. Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), members of the Herpesviridae family (17), possess large DNA genomes, share virion structures and replication mechanisms, and establish lifelong latency in host cells. The HSV genome comprises a 152-kb double-stranded DNA molecule that encodes approximately 80 gene products expressed in a temporally regulated cascade (6, 68). HSV genes are classified into three groups: immediate-early, early, and late genes. Immediate-early genes are expressed first upon infection and encode several transactivators, which in turn initiate transcription of the other early and some late genes; the latter are called leaky late or ␥1 genes (12,20,48,73). Early gene products include viral DNA replication factors that initiate viral DNA synthesis, which in turn stimulate expression of ␥1 and true late (␥2) genes, encoding mainly virion structural proteins.The immediate-early viral proteins ICP4, ICP27, ICP0, and ICP22 allow the virus to create an environment conducive to infection and counteract the intrinsic ability of cells to inhibit viral infection (29,34,55,59). ICP4 and ICP27 play essential roles in stimulating robust viral gene expression (34). The immediateearly protein ICP0 activates viral and cellular gene expression and functions as an E3 ubiquitin ligase that degrades several cellular proteins (29). ICP0 targets the promyelocytic leukemia protein (PML), a major component of nuclear foci called ND10 bodies that repress viral gene expression. ICP0 interferes with several intrinsic host defense mechanisms, including the host interferon responses (29), thereby playing a major role in establishing permissive conditions for viral infec...
Cytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion. The functional analysis of the IL-8 gene revealed that both AP-1and NF-B factor-binding elements were involved in conferring the responsiveness to CMV. Moreover, electrophoretic mobility shift assays demonstrated that CMV induced the formation of NF-B and AP-1 complexes. These results suggest that CMV activates these transcriptional factors, resulting in IL-8 gene expression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.