Reinfection Mechanisms of Various Viruses and Their Societal Implications

Review Reinfection Mechanisms of Various Viruses and Their Societal Implications Ryusuke Kimura 1,2,†, Yuriko Hayashi 3,†, Yuka Sato-Fujimoto 4, Kei Miyakawa 5, Kazuya Shirato 6, Koo Nagasawa 7, Fuminori Mizukoshi 6, Takeshi Tsugawa 8, Akihide Ryo 4 and Hirokazu Kimura 2,3,* 1 Department of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi-shi 371-8511, Gunma, Japan 2 Advanced Medical Science Research Center, Gunma Paz University, Takasaki-shi 370-0006, Gunma, Japan 3 Department of Health Science, Graduate School of Health Sciences, Gunma Paz University, Takasaki-shi 370-0006, Gunma, Japan 4 Faculty of Healthcare, Tokyo Healthcare University, Setagaya-ku 141-8648, Tokyo, Japan 5 Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Musashimurayama-shi 208-011, Tokyo, Japan 6 Department of Virology III, Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Musashimurayama-shi 208-0011, Tokyo, Japan 7 Department of Pediatrics, Chiba University Hospital, Chiba-shi 260-8670, Chiba, Japan 8 Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo-shi 060-8543, Hokkaido, Japan * Correspondence: [email protected] † These authors contributed equally to this work. Received: 27 December 2024; Revised: 22 January 2025; Accepted: 24 February 2025; Published: 26 February 2025 Abstract: Viral infections involve numerous pathogens, some of which allow reinfection while others, such as measles virus, provide lifelong immunity. The differences in reinfection mechanisms can be attributed to variations in viral antigenicity and host immune responses. Measles virus exhibits highly conserved hemagglutinin (HA) proteins, where neutralizing antibody-binding regions overlap with host receptor-binding sites, resulting in effective immune protection against reinfection. In contrast, influenza viruses undergo rapid antigenic evolution driven by immune selection pressures, leading to immune escape variants that facilitate annual reinfections. SARS-CoV-2, similarly, shows frequent mutations in its spike protein receptor-binding domain (RBD), contributing to reinfection despite prior immunity from vaccination or infection. Respiratory syncytial virus (RSV) and human respirovirus type 3 (HRV3) are monoserotype viruses capable of lifelong reinfections. Structural analyses indicate that their conformational epitopes do not align with neutralizing antibody-binding sites, undermining the effectiveness of immune responses. To better understand these mechanisms highlights the interplay between viral evolution and host defenses, providing essential insights for developing targeted vaccines and therapeutic strategies to combat respiratory virus reinfections. Moreover, understanding of the reinfection mechanisms regarding various virus infections may significantly influence public health policies, emphasizing the need for effective vaccination strategies, risk communication, and consideration of cultural factors to address challenges in vaccine adoption, health behaviors, and societal stigma.