key: cord-0284887-w9r7o3cd
authors: Chen, Dongsheng; Ou, Zhihua; Wang, Haoyu; Zhang, Yanan; Zhu, Jiacheng; An, Fuyu; Xu, Jinqian; Ding, Xiangning; Ding, Peiwen; Luo, Lihua; Wu, Weiying; Qin, Qiuyu; Wei, Yanan; Zhao, Wandong; Lv, Zhiyuan; Lan, Tianming; Li, Meiling; Zhang, Wensheng; Liu, Huan; Hua, Yan
title: Viral receptor profiles of masked palm civet revealed by single-cell transcriptomics
date: 2021-07-21
journal: bioRxiv
DOI: 10.1101/2021.07.20.452903
sha: 63fc2c30e4092318a6924635e380dabd3e7a170a
doc_id: 284887
cord_uid: w9r7o3cd

Civets are small mammals belonging to the family Viverridae. The masked palm civets (Paguma larvata) served as an intermediate host in the bat-to-human transmission of severe acute respiratory syndrome coronavirus (SARS-CoV) in 20031. Because of their unique role in the SARS outbreak, civets were suspected as a potential intermediate host of SARS-CoV-2, the etiological pathogen of the COVID-19 pandemic. Besides their susceptibility to coronaviruses, civets can also be infected by other viruses, such as canine distemper viruses2, parvoviruses3, influenza viruses4, etc. Regarding the ecological and economical role of civets, it is vital to evaluate the potential threats from different pathogens to these animals. Receptor binding is a necessary step for virus entry into host cells. Understanding the distribution of receptors of various viruses provides hints to their potential tissue tropisms. Herein, we characterized the cell atlas of five important organs (the frontal lobe, lung, liver, spleen and kidney) of masked palm civets (Paguma larvata) and described the expression profiles of receptor associated genes of 132 viruses from 25 families, including 16 viruses from 10 families reported before that can attack civets and 116 viruses with little infection record.

The receptor expressions of other viruses that have not been reported to infect civets 1 0 4 were also identified, including Adenoviridae, Arenaviridae, Flaviviridae, other receptors tended to be lower than the above-mentioned ones or concentrated in 1 1 0 certain organs (Fig. S1, Fig. S2 ). The receptor expression profiles could help us better clarify or predict the 1 1 2 pathological outcomes caused by viral infection in civets. For example, the canine 1 1 3 parvoviruses were reported to cause diarrhea and deaths in civets and the viral DNA 1 1 4 can be detected in the brain, liver, heart, spleen and small intestine 3 , which is 1 1 5 consistent with the wide distribution of its receptor TFRC in the civet organs. Lyssaviruses usually cause fatal encephalitic diseases in a wide range of mammals 1 1 7 with civet infections reported in Africa and Asia 5,6 . Our results showed an obvious 1 1 8 enrichment of a related receptor, NCAM1, in multiple cell types of the civet frontal 1 1 9 lobe, which may contribute to the neurovirulence of these viruses. The receptor of 1 2 0 SARS-CoV-2, ACE2, was only expressed at moderate levels in the kidney and flow 1 2 1 cytometric experiment showed undetectable binding between the civet ACE2 ortholog 1 2 2 and the viral receptor-binding domain. However, two alternative receptors, NRP1 and 1 2 3 AXL, were both highly expressed in the lung and spleen, indicating potential 1 2 4 susceptibility of civets to SARS-CoV-2, although in vivo infection remains unclear. Taken together, we have built a comprehensive multi-organ cell atlas of masked palm 1 2 7 civet and described the distribution of various viral receptors in these tissues, 1 2 8 providing preliminary evidence of the potential tissue tropism of these viruses in 1 2 9

civets. The results could enhance our knowledge of the biological background of 1 3 0 civets and their susceptibility to various pathogens, which may facilitate the control 1 3 1 and prevention of enzootic and zoonotic viruses. This work was supported by China National GeneBank (CNGB). Tables  1  8  4   Table S1 . Marker genes for cell types of frontal lobe, lung, liver, spleen and kidney 1 8 5 

Isolation and characterization of viruses related to the SARS coronavirus from