Abstract
Apoptosis, a form of the programmed cell death, is an indispensable defense mechanism regulating cellular homeostasis and is triggered by multiple stimuli. Because of the regulation of apoptosis in cellular homeostasis, viral proteins with apoptotic activity are particular foci of on antitumor therapy. One representative viral protein is the open reading frame 3 (ORF3) protein, also named as apoptin in the Circoviridae chicken anemia virus (CAV), and has the ability to induce tumor-specific apoptosis. Proteins encoded by ORF3 in other circovirus species, such as porcine circovirus (PCV) and duck circovirus (DuCV), have also been reported to induce apoptosis, with subtle differences in apoptotic activity based on cell types. This article is aimed at reviewing the latest research advancements in understanding ORF3 protein-mediated apoptosis mechanisms of Circoviridae from three perspectives: subcellular localization, interactions with host proteins, and participation in multiple apoptotic signaling pathways, providing a scientific basis for circovirus pathogenesis and a reference on its potential anticancer function.
Highlights
The Circoviridae family, whose members are considered to cause fatal diseases in birds and pigs, is composed of two recognized genera: Circovirus and Cyclovirus (Rosario et al, 2017)
The main histological changes associated with infections by Circoviridae family viruses are lymphoid tissues, which show with lymphocyte depletion and necrosis (Woods and Latimer, 2000; Palinski et al, 2016; Dennis et al, 2018; Klaumann et al, 2018) that may be connected to the apoptotic activity of open reading frame 3 (ORF3) proteins
The findings of Nuclear localization signals (NLSs) in chicken anemia virus (CAV) (Rohn et al, 2002), porcine circovirus (PCV) (Lin et al, 2011; Hough et al, 2015), and duck circovirus (DuCV) (Wu et al, 2018) ORF3 proteins suggest the possibility of these proteins being located in the nucleus
Summary
The Circoviridae family, whose members are considered to cause fatal diseases in birds and pigs, is composed of two recognized genera: Circovirus and Cyclovirus (Rosario et al, 2017). For PCV, a Rep’ protein can be generated by alternative transcript splicing of ORF1, and the Rep-Rep’ complex is required for promoting virus replication by RCR system (Steinfeldt et al, 2002). In addition to the Rep and Cap, ORF3 of Circovirus encodes a protein that can participate in cell death during viral infection. In Cyclovirus, reports have implicated that ORF3 encodes a nonstructural protein and participates in the induction of apoptosis and viral cytotoxicity in host cells (Kucharski et al, 2016) (Figure 1A)
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