Faculty Profile, National Health Research Institutes, Taiwan

Faculty Profiles


Huan-Yao Lei, Ph.D.

Joint-appointed Investigator
Division of Infectious Diseases
hylei@mail.ncku.edu.tw

EDUCATION

-Ph.D., Immunology, Department of Microbiology & Immunology, Northwestern University, U.S.A.
-B. S., Department of Agricultural Chemistry National Taiwan University, Taiwan

PROFESSIONAL EXPERIENCES

- Chairman & Professor, Institute of Basic Medical Sciences, College of Medicine, Cheng-Kung University, Taiwan (2004-present)
- Chairman & Professor, Department of Microbiology & Immunology, College of Medicine, Cheng-Kung University, Taiwan (1994-2000)
- Professor, Department of Microbiology & Immunology, College of Medicine, Cheng-Kung University, Taiwan (1990-present)
- Associate Professor, Department of Microbiology & Immunology, College of Medicine, Cheng-Kung University, Taiwan (1985-1990)
- Instructor, Department of Microbiology & Immunology, College of Medicine, Cheng-Kung University, Taiwan (1983-1985)

RESEARCH INTERESTS

Dengue virus infection causes a broad spectrum of disease from mild dengue fever to severe dengue hemorrhagic fever/dengue shock syndrome. Dengue virus infection would also induce autoimmunity. The immunopathogenesis, and the role of antibody-dependent enhancement in dengue virus infection are the aims that we target.

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Dengue virus infection causes a broad spectrum of disease from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF).. It is generally estimated that 24% of dengue virus infected person become DF, with 6% progress into DHF and 1-2% death. The progression from DF into DHF is not predictable and the treatment is limited, with only supportive care of blood fluid supplement. Currently, no commercial dengue vaccines are available. We have studied two important issues related to the role of antibody in the dengue virus infection will be addressed. First is the immunopathogenesis of dengue virus infection. We found that the Dengue virus infection could induce immune aberrant activation and cytokine overproduction. Anti-dengue antibodies can cross-react with platelets and endothelial cells due to molecular mimicry between dengue virus and self. A new hypothesis of immunopathogenesis for dengue virus infection was proposed. Dengue virus infection induces autoimmunity of auto anti-platelet and anti-endothelial cell antibody. Together with IFN-g activated macrophage to develop a hemophagocytic-like syndrome in dengue disease. The immune memory or immune enhancement in secondary infection can boost more immune deviation, more autoantibody with high affinity or more cytokine overproduction. This immunopathogenesis of DHF/DSS can account for specific characteristic of clinical, pathologic and epidemiological observations in dengue virus infection. Second, we have studied the role of antibody-dependent enhancement (ADE) of infection in the dengue virus infection. The non-neutralizing anti-dengue antibody bound to dengue virion enhanced the virus entrance into target cells via Fc receptor. We found that enhancing antibody not only enhanced the percentage of dengue-infected cells, but also increased the viral replication in the cells. The enhancement is dependent on the types of the target cells and the specificity of the enhancing antibody. The enhancing antibody can be either anti-prM or anti-E antibody. For anti-E Ab-mediated enhancement on monocytic cells, it can be concentration-dependent: enhancing at sub-neutralization level or enhance regardless of concentration by Fc and FcR interaction. For anti-prM Ab-mediated enhancement, it enhanced the dengue virion binding on both FcR or non-FcR bearing cells with dual specificity. Understanding the mechanism of DHF immunopathogenesis and ADE will not only help the treatment of dengue patient especially in the adult, but also provide a challenge to develop the safe and effective dengue vaccine in the future.

SELECTED PUBLICATIONS

1.Lee WC, Lien KY, Lee GB and Lei HY. An integrated microfluidic system using magnetic beads for virus detection. Diag. Micro. Infect. Dis., 60: 5158, 2008.
2.Huang KJ, Yang YC, Lin YS, Huang JH, Liu HS, Yeh TM, Chen SH, Liu CC and Lei HY. The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection. J. Immunol., 176: 2825-2832, 2006.
3.Hung NT, Lei HY, Lan NR, Lin YS, Huang KJ, Lien LB, Lin CF, Yeh TM, Ha DQ, Huong VTQ, Chen LC, Huang JH, My LT, Liu CC and Halstead SB. Dengue hemorrhagic fever in infants: A study on clinical and cytokine profiles. J. Infect. Dis., 189:221-232, 2004.
4.Liu CC, Huang KJ, Lin YS, Yeh TM, Liu HS and Lei HY. Transient CD4/CD8 ratio inversion and immune deviation during dengue virus infection. J. Med. Virol., 68:241-252, 2002.
5.Lei HY, Yeh TM, Liu HS, Lin YS, Chen SH and Liu CC. Immunopathogenesis of dengue virus infection J. Biomed. Sci., 8:377-388, 2001.