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27The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel 28 coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated 29 with a seafood market in Wuhan, China, where the sale of wild animals may be the source of 30 zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of 31 any intermediate host facilitating transfer to humans is unknown. Here, we report the 32 identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in 33 anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin 34 associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, 35 including one very closely related to 2019-nCoV in the receptor-binding domain. The 36 discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV 37 suggests that pangolins should be considered as possible intermediate hosts for this novel 38 human virus and should be removed from wet markets to prevent zoonotic transmission.

Highlights d Six high-quality ixodid tick genomes and 678 re-sequenced tick specimens d Insights into the genetic basis of tick hematophagy and related phenotypes d Population structure and genetic diversity of six tick species d Tick-borne pathogen composition and distribution by metagenome analyses

Background A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. Methods We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection. Findings A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China. Interpretation The public significance of JMTV should be highly concerning due to its potential pathogenicity for humans and efficient transmission by potential ticks. Fund China Natural Science Foundation, State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.

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