Abstract
Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Further investigations revealed that oncoVV-TTL replication was highly dependent on ERK activity. This study might provide insights into a novel way of the utilization of TTL in oncolytic viral therapies.
Highlights
The horseshoe crab, as a “living fossil”, has survived for more than 500 million years [1].It can live solely on its hemolymph that contains granular hemocytes comprising 99% of the total hemocytes
We investigated the effect of oncolytic vaccinia virus (oncoVV)-tridentatus Lectin (TTL) on cellular levels of mitochondrial antiviral signaling protein (MAVS) and interferon-inducible protein 16 (IFI16)
Our results indicated that TTL favors oncolytic vaccinia virus replication through suppressing the antiviral response of cancer cells
Summary
The horseshoe crab, as a “living fossil”, has survived for more than 500 million years [1]. It can live solely on its hemolymph that contains granular hemocytes comprising 99% of the total hemocytes. The granules store many soluble defense molecules, such as lectins, clotting factors, clottable protein coagulogens, and C-reactive proteins [2,3]. Lectins play diverse roles in physiological processes [6,7], including mediating interactions between cells during development and differentiation [8], and recognizing foreign molecules during immune responses [9]. Several lectins with a broad range of specificity have been identified in horseshoe crab [10]. In the Japanese horseshoe crab, there are six types of lectins, Tachylectin-1 (TL-1), Tachylectin-2
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