Figure 1. Structure of reovirus

Reoviridae is one of the most widely distributed viral families. Mammalian orthoreovirus (MRV), belonging to the genus Orthoreovirus, primarily infects the respiratory and intestinal tracts of mammals. The complete viral particle is icosahedral, approximately 60-80 nm in diameter, and lacks an envelope. The viral genome, approximately 18-27 kb, is enclosed by a double-layered protein capsid (Figure 1).

MRVs are classified into three serotypes based on their red blood cell agglutination activity: serotype 1 (T1L, Long), serotype 2 (T2J, Jone), and serotype 3 (T3D, Dearing; T3A, Abney). Wild-type or modified ReVs exert oncolytic effects through the following mechanisms: 1) they can replicate extensively within tumor cells, leading to direct lysis of the tumor cells; 2) infection of tumor cells leads to the release of viral progeny, cytokines, and tumor-associated antigens (TAAs), thereby initiating innate anti-tumor immunity, including cytokine-mediated killing and natural killer (NK) cell-mediated cytotoxicity; 3) dendritic cells (DCs) present TAAs to CD4+ and CD8+ T cells, triggering adaptive anti-tumor immune responses (Figure 2). In clinical studies, wild-type ReVs are primarily used in combination with other anticancer therapies.

Figure 2. Mechanism of action of reovirus (PMID: 33142841)