Expertise
- Molecular virology
- Virus-cell interactions
- Innate immunity, antiviral signaling
- Vaccine development
RESEARCH FOCUS
- Molecular virology of porcine reproductive and respiratory syndrome virus (PRRSV), hepatitis E virus (HEV), Zika virus and others.
- Viral pathogenesis and virus-cell interactions
- Mechanisms of viral interference of host innate immunity - Interferon induction and downstream signaling
- Development of effective vaccines and novel antiviral therapeutics
Viruses are infectious agents that replicate inside the cells, like obligate intracellular parasites. To invade the host, viruses must overcome antiviral defense and induce a conducive environment for their own replication and spread. To prevent and control invading pathogens, the host has developed various strategies, including innate and adaptive immunity. The virus-cell interactions are complex, and the context of the interactions may determine the consequence of the viral infection. Dr. Zhang’s research interests are on molecular virology, virus-cell interactions, viral pathogenesis, and vaccine development. His current projects are on positive-sense RNA viruses, including hepatitis E virus (HEV), porcine reproductive and respiratory syndrome virus (PRRSV), and Zika virus (ZIKV). HEV is the causative agent of endemic and epidemic acute human hepatitis in many parts of the world. It is a zoonotic infectious agent that has been identified in swine, rat, rabbit, chicken, and deer. We have discovered that HEV ORF1 product blocks interferon induction and that HEV ORF3 product increases RIG-I level and activates RIG-I signaling. PRRSV has been causing heavy economic losses to the swine industry worldwide since it was first reported in 1987. An improved vaccine is needed to prevent and control the disease. ZIKV is a mosquito-borne flavivirus, which has drawn public attention due to its association with severe microcephaly in newborns and Guillain-Barre syndrome (GBS) in adults. Dr. Zhang’s lab is conducting research on elucidating mechanisms of viral replication in the host cells, viral interference with the innate immunity, especially interferon production and interferon-activated JAK-STAT signaling, and other aspects of virus-cell interactions. His lab has discovered that PRRSV inhibits the signaling of STAT1, STAT2, and STAT3. His lab also studies karyopherins, which are a group of proteins mediating the nucleocytoplasmic trafficking of numerous proteins including those transcription factors involved in host defense. He is also interested in vaccine development against PRRSV, and his team discovers a novel PRRSV strain that is able to induce interferon production. This strain elicits earlier onset and higher virus-neutralizing antibodies. Further research on the strain is undertaken to develop an improved vaccine against PRRSV infection.
Selected Publications
He, J; Yang, .; Chang, P; Yang, S; Wang, Y; Lin, S; Tang, Q; and Zhang, Y. Zika Virus Induces
the Degradation of the Numb Protein that is Required through Embryonic Neurogenesis. Viruses
2023, 15(6), 1258; https://doi.org/10.3390/v15061258.
Lin S and Zhang YJ. Advances in Hepatitis E Virus Biology and Pathogenesis. Viruses 2021,
13(2), 267; https://doi.org/10.3390/v13020267.
He J, Yang L, Chang P, Yang S, Lin S, Tang Q, Wang X, and Zhang YJ. Zika virus NS2A
protein induces the degradation of KPNA2 (karyopherin subunit alpha2) via chaperone-mediated
autophagy. Autophagy. 2020 Dec;16(12):2238-2251. doi: 10.1080/15548627.2020.1823122.
Yang L, He J, Wang R, Zhang X, Ma Z, and Zhang YJ: Porcine reproductive and respiratory
syndrome virus inhibits STAT2 signaling via nsp11-mediated downregulation. J Virol 2019 Aug
28. pii: JVI.01352-19. doi: 10.1128/JVI.01352-19.
Lin S, Yang S, He J, Guest JD, Ma Z, Yang L, Pierce BG, Tang Q, Zhang YJ.2. Zika virus NSS
protein antagonizes type I interferon production via blocking TBK1 activation. Virology. 2019
Jan 15;527:180-187. doi: 10.1016/j.virol.2018.11.009.
Yang L, Wang R, Yang S, Ma Z, Lin S, Nan Y, Li Q, Tang Q, Zhang YJ. Karyopherin Alpha 6 Is
Required for Replication of Porcine Reproductive and Respiratory Syndrome Virus and Zika.
Virus. J Virol. 2018 May 1;92(9). doi: 10.1128/JVI.00072-18.
Yang L, Wang R, Ma Z, Xiao Y, Nan Y, Wang Y, Lin S, Zhang YJ. Porcine Reproductive and.
Respiratory Syndrome Virus Antagonizes JAK/STAT3 Signaling via nsp5, Which Induces
STAT35. Degradation.J Virol. 2017 Feb 1;91(3). doi: 10.1128/JVI.02087-16.
Ma Z, Yu Y, Xiao Y, Opriessnig T, Wang R, Yang L, Nan Y, Samal SK, Halbur PG, Zhang YJ.
Sustaining Interferon Induction by a High. Passage Atypical Porcine Reproductive and.
Respiratory Syndrome Virus Strain. Sci Rep. 2016 Nov 2;6:36312. doi: 10.1038/srep36312.
Nan Y, Yu Y, Ma Z, Khattar SK, Fredericksen B, Zhang YJ. Hepatitis E virus inhibits type
I.interferon induction by ORF1 products. J Virol. 2014 Oct;88(20):11924-32.
doi:10.1128/JVI.01935-14.
Wang R, Nan Y, Yu Y, Zhang YJ. Porcine reproductive and respiratory syndrome virus Nsp1β8.
inhibits interferon. activated JAK/STAT signal transduction by inducing karyopherin α18.
degradation.J Virol. 2013 May;87(9):5219-28. doi: 10.1128/JVI.02643-12.
Patel D, Nan Y, Shen M, Ritthipichai K, Zhu X, Zhang YJ. Porcine reproductive and respiratory.
syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear.
translocation. J Virol. 2010 Nov;84(21):11045-55. doi: 10.1128/JVI.00655-10.
Kannan H, Fan S, Patel D, Bossis I, Zhang YJ. The hepatitis E virus open reading frame 310.
product interacts with microtubules and interferes with their dynamics. J Virol. 2009
Jul;83(13):6375-82. doi: 10.1128/JVI.02571-08.
