Research Area
My research focuses on the understanding of host innate immune recognition and restriction of viral infection and exploring the utility of genome editing and other technologies in eradicating and curing viral diseases including AIDS. Our main discoveries include host innate immune recognition of viral PAMP, the anti-viral activities of interferon stimulated genes (ISGs). We have also reported the utility of CRISPR/Cas genome editing system inhibiting virus replication, and the unique resistance mechanism allowing HIV to escape from CRISPR/Cas9 attack.
Team Description
I am a principle investigator at Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Our main discoveries include host innate immune recognition of viral PAMP, the anti-viral activities of interferon stimulated genes. We have also reported the utility of CRISPR/Cas genome editing system inhibiting virus replication, and the unique resistance mechanism allowing HIV to escape from CRISPR/Cas9 attack. We believe in and strive to harness the power of host innate immune response and CRISPR/Cas genome editing technology toward the control of severe infectious diseases.
Team Members
Team Show
Publications
CRISPR/Cas:
1. CRISPR-Cas13a Inhibits HIV-1 Infection. Yin L, Zhao F, Sun H, Wang Z, Huang Y, Zhu W, Xu F, Mei S, Liu X, Zhang D, Wei L, Cen S, Hu S, Liang C, Guo F. Mol Ther Nucleic Acids. 2020 Jun 1;21:147-155. doi: 10.1016/j.omtn.2020.05.030.
2. CRISPR/Cas9 Inhibits Multiple Steps of HIV-1 Infection. Yin L, Hu S, Mei S, Sun H, Xu F, Li J, Zhu W, Liu X, Zhao F, Zhang D, Cen S, Liang C, Guo F. Hum Gene Ther. 2018 Nov;29(11):1264-1276
3. HIV-1 employs multiple mechanisms to resist Cas9/sgRNA targeting the viral primer binding site. Wang Z, Wang W, Cui YC, Pan Q, Zhu W, Gendron P, Guo F, Cen S, Witcher M, Liang C. J Virol. 2018 Aug 1. pii: JVI.01135-18. doi: 10.1128/JVI.01135-18.
4. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S, Wainberg MA, Liang C. Cell reports 2016：15, 1–9.
5. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Zhu W, Lei R, Le Duff Y, Li J, Guo F, Wainberg MA, Liang C. Retrovirology. 2015 Feb 27;12(1):22. doi: 10.1186/s12977-015-0150-z.
Innate immune recognition and restriction factors:
6. A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA. Sun H,Yu Huang, Mei S, Xu F, Liu X, Zhao F, Yin L, Zhang D, Wei L, Wu C, Ma S, Wang J, Cen S, Liang C, Hu S, Guo F. Cell Reports, 2021
7. HIV-1 resists MxB inhibition of viral Rev protein. Wang Z, Chai K, Liu Q, Yi DR, Pan Q, Huang Y, Tan J, Qiao W, Guo F, Cen S, Liang C. Emerg Microbes Infect. 2020 Sep 1:1-44. doi: 10.1080/22221751.2020.1818633. Online ahead of print. PMID: 32873191
8. Activation and evasion of type I interferon responses by SARS-CoV-2. Lei X, Dong X, Ma R, Wang W, Xiao X, Tian Z, Wang C, Wang Y, Li L, Ren L, Guo F, Zhao Z, Zhou Z, Xiang Z, Wang J. Nat Commun. 2020 Jul 30;11(1):3810. doi: 10.1038/s41467-020-17665-9.
9. Chemokine (C-X-C motif) Ligand 4 is a Restrictor of Respiratory Syncytial Virus Infection and an Indicator of Clinical Severity. Han Z, Rao J, Xie Z, Wang C, Xu B, Qian S, Wang Y, Zhu J, Yang B, Xu F, Lei X, Guo F, Zhao Z, Ren L, Wang J. Am J Respir Crit Care Med. 2020 Jun 16. doi: 10.1164/rccm.201908-1567OC.
10. Pro-515 of the Dynamin-Like GTPase MxB Contributes to HIV-1 Inhibition by Regulating MxB Oligomerization and Binding to HIV-1 Capsid. Xu F, Zhao F, Zhao X, Zhang D, Liu X, Hu S, Mei S, Fan Z, Huang Y, Sun H, Wei L, Wu C, Li Q, Wang J, Cen S, Liang C, Guo F. J Biol Chem. 2020 May 8;295(19):6447-6456. doi: 10.1074/jbc.RA119.012439. Epub 2020 Mar 26.
11. PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing. Hu S, Sun H, Yin L, Li J, Mei S, Xu F, Wu C, Liu X, Zhao F, Zhang D, Huang Y, Ren L, Cen S, Wang J, Liang C, Guo F. Sci Signal. 2019 Nov 26;12(609). pii: eaav7934. doi: 10.1126/scisignal.aav7934.
12. Influenza Virus Exploits an Interferon-Independent lncRNA to Preserve Viral RNA Synthesis through Stabilizing Viral RNA Polymerase PB1. Wang J, Zhang Y, Li Q, Zhao J, Yi D, Ding J, Zhao F, Hu S, Zhou J, Deng T, Li X, Guo F, Liang C, Cen S. Cell Rep. 2019 Jun 11;27(11):3295-3304.e4. doi: 10.1016/j.celrep.2019.05.036
13. MOV10 sequesters the RNP of influenza A virus in the cytoplasm and is antagonized by viral NS1 protein. Li J, Hu S, Xu F, Mei S, Liu X, Yin L, Zhao F, Zhao X, Sun H, Xiong Z, Zhang D, Cen S, Wang J, Liang C, Guo F. Biochem J. 2019 Feb 5;476(3):467-481. doi: 10.1042/BCJ20180754.
14. Human MxB inhibits the replication of HCV. Yi DR, An N, Liu ZL, Xu FW, Raniga K, Li QJ, Zhou R, Wang J, Zhang YX, Zhou JM, Zhang LL, An J, Qin CF, Guo F, Li XY, Liang C, Cen S. J Virol. 2018 Oct 17. pii: JVI.01285-18. doi: 10.1128/JVI.01285-18.
15. Host Long Noncoding RNA lncRNA-PAAN Regulates the Replication of Influenza A Virus. Wang J, Wang Y, Zhou R, Zhao J, Zhang Y, Yi D, Li Q, Zhou J, Guo F, Liang C, Li X, Cen S. Viruses. 2018 Jun 16;10(6). pii: E330. doi: 10.3390/v10060330
16. Identification of small molecule compounds targeting the interaction of HIV-1 Vif and human APOBEC3G by virtual screening and biological evaluation. Ma L, Zhang Z, Liu Z, Pan Q, Wang J, Li X, Guo F, Liang C, Hu L, Zhou J, Cen S. Sci Rep. 2018 May 23;8(1):8067. doi: 10.1038/s41598-018-26318-3
17. A highly conserved amino acid in VP1 regulates maturation of enterovirus 71. Zhang YX, Huang YM, Li QJ, Li XY, Zhou YD, Guo F, Zhou JM, Cen S. PLoS Pathog. 2017 Sep 22;13(9):e1006625.
18. Identification and characterization of loop7 motif and its role in regulating biological function of human APOBEC3G through molecular modeling and biological assay. Zhai C, Ma L, Zhang Z, Ding J, Wang J, Zhang Y, Li X, Guo F, Yu L, Zhou J, Cen S. Acta Pharm Sin B. 2017 Sep;7(5):571-582. doi: 10.1016/j.apsb.2017.05.002. Epub 2017 Jun 2.
19. BST-2 restricts IAV release and is countered by the viral M2 protein. Hu S, Yin L, Mei S, Li J, Xu F, Sun H, Liu X, Cen S, Liang C, Li A, Guo F. Biochem J. 2017 Feb 20;474(5):715-730. doi: 10.1042/BCJ20160861.
20. Distribution and characteristics of rodent picornaviruses in China. Du J, Lu L, Liu F, Su H, Dong J, Sun L, Zhu Y, Ren X, Yang F, Guo F, Liu Q, Wu Z, Jin Q. Sci Rep. 2016 Sep 29;6:34381. doi: 10.1038/srep34381.
21. Amphotericin B Inhibits Enterovirus 71 Replication by Impeding Viral Entry. Xu F, Zhao X, Hu S, Li J, Yin L, Mei S, Liu T, Wang Y, Ren L, Cen S, Zhao Z, Wang J, Jin Q, Liang C, Ai B, Guo F. Sci Rep. 2016 Sep 9;6:33150.
22. 2-thio-6-azauridine inhibits Vpu mediated BST-2 degradation. Zhang Q, Mi Z, Huang Y, Ma L, Ding J, Wang J, Zhang Y, Chen Y, Zhou J, Guo F, Li X, Cen S. Retrovirology. 2016 Mar 2;13(1):13. doi: 10.1186/s12977-016-0247-z.
23. Stress out the LINEs. Hu S, Liang C, Guo F. Mob Genet Elements. 2015 Dec 29;6(1):e1133267.
24. A small molecule compound IMB-LA inhibits HIV-1 infection by preventing viral Vpu from antagonizing the host restriction factor BST-2. Mi Z, Ding J, Zhang Q, Zhao J, Ma L, Yu H, Liu Z, Shan G, Li X, Zhou J, Wei T, Zhang L, Guo F, Liang C, Cen S. Sci Rep. 2015 Dec 16;5:18499. doi: 10.1038/srep18499.
25. SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation. Hu S, Li J, Xu F, Mei S, Le Duff Y, Yin L, Pang X, Cen S, Jin Q, Liang C and Guo F. PLoS Genet. 2015 Jul 2;11(7):e1005367. doi: 10.1371/ journal.pgen.1005367. eCollection 2015 Jul.
26. Characterization of the interactions between SIVrcm Vpx and red-capped mangabey SAMHD1. Li J, Xu F, Hu S, Zhou J, Mei S, Zhao X, Cen S, Jin Q, Liang C, Guo F. Biochem J. 2015 Jun 1;468(2):303-13. doi: 10.1042
27. Human APOBEC3F incorporation into human immunodeficiency virus type 1 particles.Wang X, Li X, Ma J, Zhang L, Ma L, Mi Z, Zhou J, Guo F, Kleiman L, Cen S. Virus Res. 2014 Oct 13;191:30-8.
28. The role of A-kinase anchoring protein 95-like protein in annealing of tRNALys3 to HIV-1 RNA.Xing L, Zhao X, Guo F, Kleiman L.Retrovirology. 2014 Jul 17;11:58. doi: 10.1186/1742-4690-11-58.
29. Identification of an endocytic signal essential for the antiviral action of IFITM3. Jia R, Xu F, Qian J, Yao Y, Miao C, Zheng YM, Liu SL, Guo F, Geng Y, Qiao W, Liang C. Cell Microbiol. 2014 Jul;16(7):1080-93. doi: 10.1111/cmi.12262. Epub 2014 Feb 13.
30. The interferon-inducible MxB protein inhibits HIV-1 infection. Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C. Cell Host Microbe. 2013 Oct 16;14(4):398-410. doi: 10.1016/j.chom.2013.08.015.
31. The roles of APOBEC3G complexes in the incorporation of APOBEC3G into HIV-1. Ma J, Li X, Xu J, Zhang Q, Liu Z, Jia P, Zhou J, Guo F, You X, Yu L, Zhao L, Jiang J, Cen S. PLoS One. 2013 Oct 2;8(10):e74892. doi: 10.1371/journal.pone.0074892.
32. Identification of novel key amino acids at the interface of the transmembrane domains of human BST-2 and HIV-1 Vpu. Pang X, Hu S, Jian Li, Xu F, Mei S, Zhou J, Cen S, Jin Q, and Guo F. Retrovirology. 2013 Aug 6;10:84. doi: 10.1186/1742-4690-10-84..
33. The MOV10 helicase inhibits LINE-1 mobility. Li X, Zhang J, Jia R, Cheng V, Xu X, Qiao W, Guo F, Liang C, Cen S.J Biol Chem. 2013 Jul 19;288(29):21148-60. doi: 10.1074/jbc.M113.465856.
34. The role of the structural domains of human BST-2 in inhibiting the release of xenotropic murine leukemia virus-related virus. Hu S, Pang X, Li J, Cen S, Jin Q, Guo F. Biochem Biophys Res Commun. 2012 Nov 9;428(1):17-23. doi: 10.1016/j.bbrc.2012.10.001. Epub 2012 Oct 6
35. From promoting to inhibiting: diverse roles of helicases in HIV-1 Replication. Lorgeoux RP, Guo F, Liang C. Retrovirology. 2012 Sep 28;9:79. doi: 10.1186/1742-4690-9-79.
36. Transmembrane interactions of HIV-1 Vpu and tetherin. Guo F, Liang C. Curr HIV Res. 2012 Jun;10(4):292-7. Review
37. High-throughput assay to identify inhibitors of Vpu-mediated down-regulation of cell surface BST-2. Zhang Q, Liu Z, Mi Z, Li X, Jia P, Zhou J, Yin X, You X, Yu L, Guo F, Ma J, Liang C, Cen S. Antiviral Res. 2011 Sep;91(3):321-9.
38. Functional analysis of the two cytidine deaminase domains in APOBEC3G. Li X, Ma J, Zhang Q, Zhou J, Yin X, Zhai C, You X, Yu L, Guo F, Zhao L, Li Z, Zeng Y, Cen S. Virology. 2011 Jun 5;414(2):130-6. doi: 10.1016/j.virol.2011.03.014. Epub 2011 Apr 13.
39. The contribution of the primer activation signal to differences between Gag- and NCp7-facilitated tRNA(Lys3) annealing in HIV-1. Saadatmand J, Niu M, Kleiman L, Guo F. Virology. 2009 Sep 1;391(2):334-41.
40. ROLES OF GAG AND NCp7 IN FACILITATING tRNALys3 ANNEALING TO VIRAL RNA IN HIV-1. Guo F, Saadatmand J, Niu M, Kleiman L. J Virol. 2009 Aug;83(16):8099-107.
41. The Transmembrane Domain of BST-2 Determines Its Sensitivity to Down-Modulation by HIV-1 Vpu. Rong L, Zhang J, Lu J, Pan Q, Lorgeoux RP, Aloysius C, Guo F, Liu SL, Wainberg MA, Liang C. J Virol. 2009 Aug;83(15):7536-46.
42. Methods for analysis of incorporation and annealing methods for analysis of tRNA(Lys) in HIV-1. Cen S, Guo F, Kleiman L. Methods Mol Biol. 2009;485:223-32.
43. Interactions of reverse transcriptase sequences in Pol with Gag and LysRS in the HIV-1 tRNALys packaging/annealing complex. Saadatmand J, Guo F，Niu M, Kleiman L. Virology, 2008 Oct 10;380(1):109-17.
44. Function analysis of sequence inhuman APOBEC3G involved in Vif-mediated degradation. Zhang L, Saadatmand J, Li XY, Guo F, Niu M, Lawrence K, Cen S. Virology, 2008 Jan 5;370(1):113-21.
45. APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. Li XY, Guo F, Zhang L, Kleiman L, Cen S. J Biol Chem. 2007 Nov 2;282(44):32065-74.)
46. The interaction of APOBEC3G with HIV-1 nucleocapsid inhibits tRNALys3 annealing to viral RNA. Guo F, Cen S, Niu M, Yang Y, Gorelick RJ, Kleiman L. J Virol. 2007 Oct;81(20):11322-31.
47. Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F. Yang Y, Guo F, Cen S, Kleiman L. Virology. 2007 Aug 15;365(1):92-100.
48. Inhibition of formula-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication. Guo F, Cen S, Niu M, Saadatmand J, Kleiman L. J Virol. 2006 Dec;80(23):11710-22.
49. Association of RNA helicase A with human immunodeficiency virus type 1 particles. Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C. J Biol Chem. 2006 May 5;281(18):12625-35.
50. Defective replication in HIV-1 using non-tRNALys3 primers for reverse transcription. Wei, M., Cen, S., Niu, M., Guo, F., Kleiman, L. J Virol. 2005 Jul;79(14):9081-7.
51. Inhibition of cellular HIV-1 protease activity by LYSYL-tRNA synthetase. Guo, F, Gabor J, Cen S, Hu K, Mouland A, Kleiman L. J Biol Chem. 2005 Jul 15;280(28):26018-23.
52. The interaction between HIV-1 Gag and APOBEC3G. Cen S, Guo, F, Niu M, Saadatmand J, Deflassieux J, Kleiman L. J Biol Chem. 2004 Aug 6;279(32):33177-84
53. Galpha protein selectivity determinant specified by a viral chemokine receptor-conserved region in the C tail of the human herpesvirus 8 g-protein-coupled receptor. Liu C, Sandford G, Fei Guo, Nicholas J. J Virol. 2004: 78(5):2460-71
54. Incorporation of pol into HIV-1 Gag VLPs Occurs independently of Upstream Gag Domain in Gagpol. Cen S, Niu M, Saadatmand J, Guo, F, Huang Y, Nabel GJ and L. Kleiman. J Virol 2004 Jan;78(2):1042-9 .
55. Specific Inhibition of the Synthesis of Human LysRS Result in Decreases in tRNAlys Incorporation, tRNAlys Annealing to Viral RNA, and Viral infectivity in Human immunodeficiency Virus-1. Guo, F, Cen S, Niu M, Javanbakht, J., and L. Kleiman..J Virol 2003 Sep;77(18):9817-22.