Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats

Dan Lu; Kefang Liu; Di Zhang; Can Yue; Qiong Lu; Hao Cheng; Liang Wang; Yan Chai; Jianxun Qi; Lin-Fa Wang; George F Gao; William J Liu

doi:10.1371/journal.pbio.3000436

Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats

PLoS Biol. 2019 Sep 9;17(9):e3000436. doi: 10.1371/journal.pbio.3000436. eCollection 2019 Sep.

Authors

Dan Lu¹, Kefang Liu^{1

2}, Di Zhang¹, Can Yue^{1

3}, Qiong Lu⁴, Hao Cheng⁵, Liang Wang⁶, Yan Chai⁶, Jianxun Qi⁶, Lin-Fa Wang⁷, George F Gao^{1

2

5

6}, William J Liu¹

Affiliations

¹ NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
² Faculty of Health Sciences, University of Macau, Macau SAR, China.
³ Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁴ Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China.
⁵ Beijing Institutes of Life Science, University of Chinese Academy of Sciences, Beijing, China.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁷ Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.

Abstract

Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC) I Ptal-N*01:01-binding peptides derived from four different bat-borne viruses, i.e., Hendra virus (HeV), Ebola virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), and H17N10 influenza-like virus. The structures of Ptal-N*01:01 display unusual peptide presentation features in that the bat-specific 3-amino acid (aa) insertion enables the tight "surface anchoring" of the P1-Asp in pocket A of bat MHC I. As the classical primary anchoring positions, the B and F pockets of Ptal-N*01:01 also show unconventional conformations, which contribute to unusual peptide motifs and distinct peptide presentation. Notably, the features of bat MHC I may be shared by MHC I from various marsupials. Our study sheds light on bat adaptive immunity and may benefit future vaccine development against bat-borne viruses of high impact on humans.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen Presentation*
Chiroptera / immunology*
Chiroptera / virology
Histocompatibility Antigens Class I / physiology*
Host-Pathogen Interactions / immunology*
RNA Viruses / immunology*

Substances

Histocompatibility Antigens Class I

Grants and funding

This work was supported by grants from Natural Science Foundation of China (NSFC), http://www.nsfc.gov.cn/ (grant number 81971501), the National Key Research and Development Program of China, http://program.most.gov.cn/# (grant number 2017YFC1200202), State's Key Project of Research and Development Plan, International Cooperation in Science and Technology Innovation, http://program.most.gov.cn/# (grant number 2016YFE0205800), and the Major Special Projects for Infectious Disease Research of China, http://www.nmp.gov.cn/ (grant number 2016ZX10004222-003). WJL is supported by the Excellent Young Scientist Program of the NSFC, http://www.nsfc.gov.cn/ (grant number 81822040). GFG is a leading principal investigator of the NSFC Innovative Research Group, http://www.nsfc.gov.cn/ (grant number 81621091). L-FW is funded in part by the Singapore National Research Foundation Grants, https://www.nrf.gov.sg/ (grant numbers NRF2012NRF-CRP001-056 and NRF2016NRF-NSFC002-013). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.