Comparative analysis of single cell lung atlas of bat, cat, tiger and pangolin (preprint)

Horseshoe bats (Rhinolophus sinicus) might help maintain coronaviruses severely affecting human health, such as SARS-CoV and SARS-CoV-2. It has long been suggested that bats may be more tolerant of viral infection than other mammals due to their unique immune system, but the exact mechanism remains to be fully explored. During the COVID-19 pandemic, multiple animal species were diseased by SARS-CoV-2 infection, especially in the respiratory system. Herein, single-cell transcriptomic data of the lungs of a horseshoe bat, a cat, a tiger, and a pangolin were generated. The receptor distribution of twenty-eight respiratory viruses belonging to fourteen viral families were characterized for the four species. Comparison on the immune-related transcripts further revealed limited cytokine activations in bats, which might explain the reason why bats experienced only mild diseases or even no symptoms upon virus infection. Our findings might increase our understanding of the immune background of horseshoe bats and their insensitivity to virus infections.

Screening of cell-virus, cell-cell, gene-gene interactions among kingdoms of life at single cell resolution (preprint)

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) issued a significant and urgent threat to global health. The exact animal origin of SARS-CoV-2 remains obscure and understanding its host range is vital for preventing interspecies transmission. Previously, we have assessed the target cell profiles of SARS-CoV-2 in pets, livestock, poultry and wild animals. Herein, we expand this investigation to a wider range of animal species and viruses to provide a comprehensive source for large-scale screening of potential virus hosts. Single cell atlas for several mammalian species (alpaca, hamster, hedgehog, chinchilla etc.), as well as comparative atlas for lung, brain and peripheral blood mononuclear cells (PBMC) for various lineages of animals were constructed, from which we systemically analyzed the virus entry factors for 113 viruses over 20 species from mammalians, birds, reptiles, amphibians and invertebrates. Conserved cellular connectomes and regulomes were also identified, revealing the fundamental cell-cell and gene-gene cross-talks between these species. Overall, our study could help identify the potential host range and tissue tropism of SARS-CoV-2 and a diverse set of viruses and reveal the host-virus co-evolution footprints.

Viral receptor profiles of masked palm civet revealed by single-cell transcriptomics (preprint)

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 2003. 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 viruses, parvoviruses, influenza viruses, 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.