Dr LU Yongxu, received his PhD from the MRC-University of Glasgow Centre for Virus Research (CVR) in the UK, under the supervision of Professor Roger Everett, where he studied the immune evasion mechanisms of herpes simplex virus. After completing his PhD in 2015, he joined the laboratory of Professor Geoffrey Smith at the University of Cambridge, as a postdoctoral researcher, focusing on novel mechanisms of poxvirus immune evasion. In 2023, he moved with Professor Geoffrey Smith to the Sir William Dunn School of Pathology at the University of Oxford to continue his research on poxviruses. Since 2025, he has served as a Researcher / Principal Investigator at the Shanghai Institute of Immunity and Infection of the Chinese Academy of Sciences.

Viral infectious diseases pose a significant threat to global public health. Viral infections can cause severe epidemics, such as smallpox, monkeypox, influenza, SARS, and COVID-19. Long-term infections can also lead to cancers, such as those caused by hepatitis B, hepatitis C, HPV, and herpesviruses. Therefore, studying viruses from virological and immunological perspectives is the only way to identify new therapeutic targets and design novel vaccines.

Poxviruses, a family of large DNA viruses, can cause severe infectious diseases, such as smallpox (with a mortality rate of up to 30%) and the recent monkeypox outbreaks in Africa, Europe, and the Americas. Due to the conserved core antigens of poxviruses, smallpox vaccines developed using different poxvirus family members successfully eradicated smallpox worldwide and provided valuable insights for developing novel recombinant vaccines.

Our research group focuses on poxviruses, employing virology, immunology, molecular biology, and vaccinology approaches to comprehensively analyse the infection process. We have identified several novel anti-poxvirus mechanisms, such as revealing that HDAC4 regulates interferon responses and HDAC5 suppresses poxvirus and herpesvirus infection and replication by modulating interferon transcription; discovering that the E3 ubiquitin ligase TRIM5 directly targets poxvirus structural proteins while activating the antiviral NF-κB signalling pathway. We also developed a novel method for identifying SARS-CoV-2 T-cell antigens using the vaccinia virus vaccine vector.

Our research will focus on the following areas:

I. Novel mechanisms of virus-host interactions.

Correspondence author and first author publications:

1.    Lu, Y.,^* Zhao, Y., Gao, C., Suresh, S., Men, J., Sawyers, A., & Smith, G. L.^* (2023). HDAC5 is a positive regulator of IRF3 activation and is targeted for degradation by protein C6 from orthopoxviruses including monkeypox virus and variola virus. Cell Reports. 43 (3). ^* shared correspondence author.

First author publications:

2.     *Zhao, Y., *Lu, Y., Richardson, S., Sreekumar, M., Albarnaz, J. D., & Smith, G. L. (2023) TRIM5α restricts poxviruses and is antagonised by CypA and viral protein C6. Nature. 620.7975 (2023): 873-880. * shared first authorship. This work leads to an investigation of new anti-viral therapy against Monkeypox

3.    *Stewart, H., *Lu, Y., … & Firth, E. (2023). The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity. iScience. 26.11 (2023): 108080. * shared first authorship.

4.      *Yin, Z., *Chen, J. L., *Lu, Y., *Wang, B., *Godfrey, L., *Mentzer, A. J., ... & Peng, Y. (2023). Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination. Cell reports, 42(5). * shared first authorship.

5.   Lu, Y., Michel, H. A., Wang, P. H., & Smith, G. L. (2022). Manipulation of innate immune signaling pathways by SARS-CoV-2 non-structural proteins. Frontiers in Microbiology, 13:1027015.

6.    Lu, Y., Stuart, J. H., Talbot-Cooper, C., Agrawal-Singh, S., Huntly, B., Smid, A. I., ... & Smith, G. L. (2019). Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses, and is degraded via vaccinia virus protein C6. Proceedings of the National Academy of Sciences, 116(24), 11997-12006.

7.   *Soday, L., *Lu, Y., *Albarnaz, J. D., Davies, C. T., Antrobus, R., Smith, G. L., & Weekes, M. P.2019). Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist. Cell Reports, 27(6), 1920-1933. * shared first authorship.

8.   Lu, Y., Orr, A., & Everett, R. D. (2016). Stimulation of the replication of ICP0-null mutant herpes simplex virus 1 and pp71-deficient human cytomegalovirus by Epstein-Barr virus tegument protein BNRF1. Journal of Virology, 90(21), 9664-9673.

9.     Lu, Y., & Everett, R. D. (2015). Analysis of the functional interchange between the IE1 and pp71 proteins of human cytomegalovirus and ICP0 of herpes simplex virus 1. Journal of virology, 89(6), 3062-3075.

Other publications: 

10.  Ravenhill, B.J., Oliveira, M., Wood, G., Di, Y., Kite, J., Wang, X., Davies, C.T., Lu, Y., Antrobus, R., Elliott, G. and Irigoyen, N., 2025. Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11. Cell Reports, 44(2).

11.  Jiao, P., Ma, J., Zhao, Y., Jia, X., Zhang, H., Fan, W., Jia, X., Bai, X., Zhao, Y., Lu, Y., Zhang, H., … Smith, G.L.& Lei, Sun. 2024. The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity. Emerging Microbes & Infections, p.2372344.

12.  Georgana, I., Scutts, S.R., Gao, C., Lu, Y., Torres, A.A., Ren, H., Emmott, E., Men, J., Oei, K. and Smith, G.L., 2024. Filamin B restricts vaccinia virus spread and is targeted by vaccinia virus protein C4. Journal of Virology, pp.e01485-23.

13.  Pallett, M.A., Lu, Y. and Smith, G.L., 2022. DDX50 Is a Viral Restriction Factor That Enhances IRF3 Activation. Viruses, 14(2), p.316.

14.  Peng, Y., Felce, S.L., Dong, D., Penkava, F., Mentzer, A.J., Yao, X., Liu, G., Yin, Z., Chen, J.L., Lu, Y. … Tao, Dong., 2021. An immunodominant NP105–113-B* 07: 02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease. Nature Immunology, pp.1-12.

15.  Zhang, Y., Gargan, S., Lu, Y. and Stevenson, N.J., 2021. An Overview of Current Knowledge of Deadly CoVs and Their Interface with Innate Immunity. Viruses, 13(4), p.560.

16.  Smith, G.L., Talbot-Cooper, C. and Lu, Y., 2018. How does vaccinia virus interfere with interferon?. Advances in Virus Research, 100, pp.355-378.

17.  Stuart, J.H., Sumner, R.P., Lu, Y., Snowden, J.S. and Smith, G.L., 2016. Vaccinia virus protein C6 inhibits type I IFN signalling in the nucleus and binds to the transactivation domain of STAT2. PLoS Pathogens, 12(12), p.e1005955.

18.  Everett, R.D., Bell, A.J., Lu, Y. and Orr, A., 2013. The replication defect of ICP0-null mutant herpes simplex virus 1 can be largely complemented by the combined activities of human cytomegalovirus proteins IE1 and pp71. Journal of Virology, 87(2), pp.978-990.