RESUMEN
The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
Asunto(s)
Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Euterios/virología , Evolución Molecular , Genoma Viral/genética , Homología de Secuencia de Ácido Nucleico , Animales , Betacoronavirus/clasificación , COVID-19 , China , Quirópteros/virología , Chlorocebus aethiops , Proteínas de la Envoltura de Coronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Proteínas M de Coronavirus , Proteínas de la Nucleocápside de Coronavirus , Reservorios de Enfermedades/virología , Genómica , Especificidad del Huésped , Humanos , Pulmón/patología , Pulmón/virología , Malasia , Proteínas de la Nucleocápside/genética , Pandemias , Fosfoproteínas , Filogenia , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , Recombinación Genética , SARS-CoV-2 , Alineación de Secuencia , Análisis de Secuencia de ARN , Glicoproteína de la Espiga del Coronavirus/genética , Células Vero , Proteínas del Envoltorio Viral/genética , Proteínas de la Matriz Viral/genética , Zoonosis/transmisión , Zoonosis/virologíaRESUMEN
Pangolin (Mains javanica) is an interesting endangered mammal with special morphological characteristics. Here, we applied proteomics and transcriptomics to explore the differentiation of pangolin skin appendages at two developmental stages and to compare gene expression profiles between abdomen hair and dorsal scale tissues. We identified 4,311 genes and 91 proteins differentially expressed between scale-type and hair-type tissue, of which 6 genes were shared by the transcriptome and proteome. Differentiation altered the abundance of hundreds of proteins and mRNA in the two types of skin appendages, many of which are involved in keratinocyte differentiation, epidermal cell differentiation, and multicellular organism development based on GO enrichment analysis, and FoxO, MAPK, and p53 signalling pathways based on KEGG enrichment analysis. DEGs in scale-type tissues were also significantly enriched in immune-related terms and pathways compared with that in hair-type tissues. Thus, we propose that pangolins have a normal skin innate immune system. Compared with the abdomen, the back skin of pangolins had more genes involved in the regulation of immune function, which may be an adaptive adjustment for the vulnerability of scaly skin to infection and injury. This investigation provides a scientific basis for the study of development and immunity of pangolin skin, which may be helpful in the protection of wild pangolin in China.