PT - JOURNAL ARTICLE AU - Seung-Ho Lee AU - Jin Sun No AU - Kijin Kim AU - Shailesh Budhathoki AU - Kyungmin Park AU - Geum Young Lee AU - Seungchan Cho AU - Hyeok Sun Choi AU - Bong-Hyun Kim AU - Seunghee Cho AU - Jong Woo Kim AU - Jin Gyeong Lee AU - Seung Hye Cho AU - Heung-Chul Kim AU - Terry A. Klein AU - Chang-Sub Uhm AU - Won-Keun Kim AU - Jin-Won Song TI - Novel Paju Apodemus Paramyxovirus 1 and 2, Harbored by <em>Apodemus agrarius</em> in The Republic of Korea AID - 10.1101/2021.03.03.433816 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.03.03.433816 4099 - http://biorxiv.org/content/early/2021/03/04/2021.03.03.433816.short 4100 - http://biorxiv.org/content/early/2021/03/04/2021.03.03.433816.full AB - Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a potential threat to public health. Currently, 78 species and 17 genera of paramyxoviruses are classified and harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Jeilongvirus has been proposed as a novel paramyxovirus genus containing J-, Beilong, and Tailam viruses, found in wild rodents. Using RT-PCR, 824 Apodemus agrarius individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was detected in 108 (13.1%) rodents captured at 14 trapping sites in Korea. We first present two genetically distinct novel paramyxoviruses (genus Jeilongvirus), Paju Apodemus paramyxoviruses 1 (PAPV-1) and 2 (PAPV-2), from A. agrarius. Six PAPV strains were completely sequenced using next-generation and Sanger sequencing. PAPV-1 genome comprised 19,716 nucleotides, with eight genes (3′-N-P/V/C-M-F-SH-TM-G-L-5′), whereas PAPV-2 genome contained 17,475 nucleotides, with seven genes (3′-N-P/V/C-M-F-TM-G-L-5′). The disparity between PAPV-1 and -2 revealed the presence of the SH gene and length of the G gene in the genome organization. The phylogenies of PAPV-1 and -2 belong to distinct genetic lineages of Jeilongvirus despite being from the same natural host. PAPV-1 clustered with Beilong and Tailam viruses, while PAPV-2 formed a genetic lineage with Mount Mabu Lophuromys virus-1. PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. Therefore, this study provides profound insights into the molecular epidemiology, virus-host interactions, and zoonotic potential of novel rodent-borne paramyxoviruses.Importance Paramyxoviruses are a critical public health and socio-economic burden to humans. Rodents play a crucial role in transmitting pathogens to humans. In the last decade, novel paramyxoviruses have been discovered in different rodents. Here, we found that Apodemus agrarius harbored two distinct genotypes of the novel paramyxoviruses, Paju Apodemus paramyxovirues 1 (PAPV-1) and 2 (PAPV-2), possessing unique genome structures that are responsible for encoding TM and G proteins of different sizes. In addition, PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III IFNs, ISGs, and proinflammatory cytokines. Thus, this study provides significant insights into molecular prevalence, virus-host interactions of paramyxoviruses. These observations raise the awareness of physicians and scientists about the emergence of new rodent-borne paramyxoviruses.Competing Interest StatementThe authors have declared no competing interest.