Novel antiviral activity of chemokines

Abstract

Antimicrobial peptides are a diverse family of small, mostly cationic polypeptides that kill bacteria, fungi and even some enveloped viruses, while chemokines are a group of mostly cationic small proteins that induce directed migration of leukocytes through interactions with a group of seven transmembrane G protein-coupled receptors. Recent studies have shown that antimicrobial peptides and chemokines have substantially overlapping functions. Thus, while some antimicrobial peptides are chemotactic for leukocytes, some chemokines can kill a wide range of bacteria and fungi. Here, we examined a possible direct antiviral activity of chemokines against an enveloped virus HSV-1. Among 22 human chemokines examined, chemokines such as MIP-1 alpha/CCL3, MIP-1 beta/CCL4 and RANTES/CCL5 showed a significant direct antiviral activity against HSV-1. It is intriguing that these chemokines are mostly known to be highly expressed by effector CD8+ T cells. The chemokines with a significant anti-HSV-1 activity commonly bound to HSV-1 virions via envelope glycoprotein gB. Electron microscopy revealed that the chemokines with a significant anti-HSV-1 activity were commonly capable of generating pores in the envelope of HSV-1. Thus, some chemokines have a significant direct antiviral activity against HSV-1 in vitro and may have a potential role in host defense against HSV-1 as a direct antiviral agent.

Vaccinia Virus Subverts a Mitochondrial Antiviral Signaling Protein-Dependent Innate Immune Response in Keratinocytes through Its Double-Stranded RNA Binding Protein, E3

“…The positive response to poly(I:C) by secretion of CCL5 attests to the presence of a TLR3-driven signaling pathway. CCL5 is a proinflammatory chemokine that has antiviral activities (51). CCL5 expression is controlled by both NF-B and IRFs (18).…”

“…The dsRNA binding domain is required for IFN resistance, interdiction of PKR signaling, broad host range in cultured cells, and virulence in animals (10,11,70). A mutant vaccinia virus in which only the Z-DNA binding domain is deleted (E3L⌬83N) displays a wild-type host range in cultured cells but has attenuated virulence (33,34,37,51). Langland et al (38) reported upregulation of a broad spectrum of proinflammatory and apoptotic genes in ⌬E3L-infected HeLa cells, while noting that infection with the E3L⌬83N virus induced a smaller subset of such genes.…”

Actinidain-hydrolyzed Type I Collagen Reveals a Crucial Amino Acid Sequence in Fibril Formation

“…Then, the glass disks were placed in 50 mM sodium phosphate buffer, pH 7.4, at 37°C to start self-assembly. After an incubation period of 10, 30, 90, or 120 min, self-assembly was stopped by placing each glass disk in 2% glutaraldehyde at room temperature for 1 h. Sample preparations for SEM observation were carried out according to the methods of Nakayama et al (34). Collagen self-assembly was observed under an S-900 ultrahigh resolution SEM (Hitachi) with an accelerating voltage of 10 kV.…”

Fusobacterium nucleatum and Human Beta-Defensins Modulate the Release of Antimicrobial Chemokine CCL20/Macrophage Inflammatory Protein 3α

“…In periodontal diseased tissue, CCL20 has been shown to be distributed in the basal layer of gingival epithelial cells (30). The protein has direct antibacterial, antifungal, and antiviral activities, again comparable to hBDs (11,37,46,61). Therefore, CCL20, along with hBDs, may play an important role in bridging the innate and adaptive immune responses.…”