Canine Parvovirus and Its Non-Structural Gene 1 as Oncolytic Agents: Mechanism of Action and Induction of Anti-Tumor Immune Response

Abstract

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models.

The Changes in Canine Parvovirus Variants over the Years

“…The CPV-2 NS1 protein has remained relatively conserved during the process of virus evolution. It is a phosphorylated protein with multiple functions, such as inducing apoptosis and promoting oncolysis [ 4 , 5 , 6 ]. The VP2 gene is 1755 bp in length and encodes 584 amino acids.…”

Antioxidant supplementation during treatment of outpatient dogs with parvovirus enteritis ameliorates oxidative stress and attenuates intestinal injury: A randomized controlled trial

“…, 2009 ). CPV-induced oxidative stress is mediated through damage of mitochondrial membrane, non-structural protein 1 (NS1) induced DNA damage besides liberation of pro-inflammatory cytokines ( Arora et al. , 2021 ).…”

Canine Parvovirus-2: An Emerging Threat to Young Pets

“…NS1 is the largest non structural protein in CPV-2, and it is primarily involved in viral replication and pathogenicity [22]. NS1 is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis by inducing an antitumor immune response in different tumor models [23]. A recent study demonstrated the amino acid residues of T598 and T601 in the C-terminal phosphorylation sites of NS1 protein, involved in replication and pathogenicity of CPV-2 [24].…”