Wenzhe Ho, MD, MPH
Professor, Pathology and Laboratory Medicine
Professor, Anatomy and Cell Biology
Professor, Center for Substance Abuse Research
Professor/Director of ABSL-III Lab, Wuhan University
Department of Pathology and Laboratory Medicine
There are four research focuses in the Ho Laboratory:
I. Innate Immunity and Viral Infections: The researchers in the Ho laboratory use molecular/cellular, biological, immunological and virological techniques to study the interactions between host cell innate immunity and HIV/HCV infections. The particular attention is paid to virus-host interactions that govern innate immune response and viral replication within a target cell. One question that is interesting most to the Ho laboratory is how HIV /HCV escape from host defense mechanisms, resulting in chronic diseases. Dr. Ho and his colleagues are now investigating how TLR-3 and RIG-I, the sensors for viral infectious and the triggers for innate immunity activation, recognize and control HIV or HCV infection/replication. These studies shall provide crucial information for the design and development of innate immunity-based treatment for patients infected with HIV and/or HCV.
II. Innate Immunity and CNS Protection: The role of the CNS innate immunity in the neuroprotection is largely undefined and under explored. It is critically important that CNS has the capacity to initiate local and effective innate immune responses against pathogens. It is now known that the CNS cells (neurons, microglia and astrocytes) are the targets for several important viruses, including HIV and HCV. Thus, to determine the mechanisms involved in the regulation of the CNS innate immunity is of importance. The recent studies by Dr Ho’s laboratory have demonstrated that resident CNS cells including human neurons express several functional toll-like receptors (TLRs), activation of which can produce antiviral cytokines (IFN-α, β and γ). Current research of the Ho laboratory is to determine the role of antiviral factors and mechanisms involved in the protection of the CNS cells (neuron, astrocytes, microglia and endothelial cells) from infection/injury caused by viruses or virus-mediated products.
III. Drugs of Abuse and HIV/HCV Infection: Since HIV and/or HCV infection are frequently found in injection drug users (IDUs) and these two pathogens are likely to be responsible for the highest infectious disease morbidity and mortality rates among IDUs, Dr. Ho’s laboratory is also investigating the role of drug abuse in the immunopathogenesis of HIV and/or HCV diseases. Dr. Ho and his research team use in vitro, ex vivo and in vivo models to directly address the question of whether drugs of abuse (Opioids, methamphetamine and alcohol) have the ability to suppress host immune responses and promote HIV and/or HCV diseases. In collaboration with the investigators from the University of Pennsylvania and Wuhan CDC in China, studies in the Ho laboratory have shown that drugs of abuse such as opioids or METH or alcohol impairs antiviral functions of host innate immune cells and facilitate HIV or HIV infection/replication. Current research in the Ho laboratory is investigating the specific effects of these drugs on IFN-mediated intracellular immunity that control HIV or HCV infection and replication. In addition, to determine whether these drugs and/or HIV impair the CNS cell function and compromise the efficacy of HIV treatment (HAART) is also a focus of Dr. Ho’s research.
IV. Innate Immunity-Based Therapy for Simian Immunodeficiency Virus (SIV) and/or Tuberculosis (TB) Infected Non-Human Primates: In coloration with the investigators at Center for Animal Experiment of Wuhan University where there is an animal biosafety laboratory, Dr. Ho and his colleagues have established non-human primate model for HIV and/or TB infection. Using these models, they are now exploring the potential of innate immunity activation-based therapy for the treatment of HIV and/or TB diseases.
1727500 Ho, W-Z., Lioy, J., Song, L., Cutilli, J.R., Polin, R.A., and Douglas, S.D.: Infection of cord blood monocyte-derived macrophages with human immunodeficiency virus type 1. J. Virol. 66:573-579, 1992.
7679409 Lioy, J., Ho*, W-Z., Cutilli, J.R., Polin, R.A., and Douglas, S.D.: Thiol suppression of human immunodeficiency virus type 1 replication in primary cord blood monocyte-derived macrophages in vitro. J. Clin. Invest. 91:495-498, 1993. *Contributed equally
8704251 Ho, W-Z., Kaufman, D., Song, L., Cutillii, J.R., and Douglas, S.D.: Cystamine inhibits human immunodeficiency virus-1 replication in cord blood-derived mononuclear phagocytes and lymphocytes. Blood. 88:928-933, 1996.
9548509 Ho, W-Z., Lai, J-P., Zhu, X.H., Uvaydova, M., and Douglas, S.D.: Human monocytes and macrophages express substance P and neurokinin-1 receptor. J. Immunol. 159:5654-5660, 1997.
9949155 Hariharan, D., Douglas, S.D., Lee, B., Lai, J-P., Campbell, D.E., and Ho, W-Z.: Interferon-gamma upregulates CCR5 expression in cord and adult blood mononuclear phagocytes. Blood. 93:1137-1144, 1999.
11274418 Lai, J-P., Ho*, W-Z., Zhan, G-X., Yi, Y., Collman, R.G., and Douglas, S.D.: Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc. Natl. Acad. Sci. U. S. A. 98:3970-3975, 2001. *Contributed equally.
12829987 Zhang, T., Li, Y., Lai, J-P., Douglas, S.D., Metzger, D.S., O'Brien, C.P., and Ho, W-Z.: Alcohol potentiates hepatitis C virus replicon expression. Hepatology 38:57-65, 2003.
15166542 Guo, C-J., Tan, N., Song, L., Douglas, S.D., and Ho, W-Z.: Alpha-defensins inhibit HIV infection of macrophages through upregulation of CC-chemokines. AIDS 18:1217-1218, 2004.
16107965 Li, Y., Wang, X., Douglas, S.D., Metzger, D.S., Woody, G., Zhang, T., Song, L., Ho, W-Z.: CD8+ T cell depletion amplifies hepatitis C virus replication in peripheral blood mononuclear cells. J. Infect. Dis. 192:1093-1101, 2005.
16175599 Zhang, T., Lin, R-T, Douglas, S.D., Yang, G., Maxcey, C., Ho, C., Lai, J-P., Wang, Y-J., and Ho, W-Z.: Hepatitis C virus inhibits intracellular interferon alpha expression in human hepatic cell lines. Hepatology 42:819-827, 2005.
16000393 Wang, X., Tan, N., Douglas, S.D., Zhang, T., Wang, Y-J., and Ho, W-Z.: Morphine inhibits the anti-HIV activity of CD8+ T cells in latently infected immune cells. J. Leukoc. Biol. 78:772-776, 2005.
16251417 Wang, C-Q., Li, Y., Douglas, S.D., Wang, X., Metzger, D.S., Zhang, T., and Ho, W-Z.: Morphine withdrawal enhances hepatitis C virus replicon expression. Am. J. Pathol. 167: 1333-1340, 2005.
16675550 Lai, J-P., Ho, W-Z., Kilpatrick, L.E., Wang, X., Kolchak, H.M., and Douglas, S.D.: Full-Length and Truncated Neurokinin-1 Receptor (NK-1R) Expression during Monocyte-Macrophage Differentiation. Proc. Natl. Acad. Sci. U. S. A. 103:7771-7776, 2006.
16933366 Zhang, T., Li, Y., and Ho, W-Z.: Drug abuse, innate immunity and HCV. Reviews in Medical Virology. 16:311-327, 2006.
17674315 Li, Y., Peng, J-S., Wang, C-Q., Zhang, T., Wan, Q., and Ho, W-Z.: Morphine inhibits intrahepatic interferon alpha expression coupled with full cycle HCV replication. J. Infect. Dis. 196:719-730, 2007.
18458095 Liang, H., Wang, W., Chen, H., Song, L., Ye, L., Wang, S-H., Wang, Y-J., and Ho, W-Z.: Methamphetamine enhances HIV-1 infection of human macrophage. Am. J. Pathol. 172:1617-1624. 2008.
19085952 Ye, L., Wang, X., Wang, S-H., Wang, Y-J., Song, L., Hou,W., Zhou L., and Ho, W-Z.: CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes. Hepatology, 49:753-762. 2008.
19015395 Wang, X., Ye, L., Zhou, Y., Hou, W., and Ho, W-Z.: Cellular microRNAs expression correlates with susceptibility of monocyte/macrophage to HIV-1 infection. Blood. 113:671-674, 2009.
19166911 Zhou, L., He, L., Wang, X., Wang, Y-J., Zhou, Y., Ye, L., Hou, W., Ho, W-Z.: Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells. Neuroscience. 159:629-637, 2009.
19193806 Hou, W., Wang, X., Ye, L., Wang, Y-J., Zhou, L., Yang, Z-Q., Riedel, E., and Ho, W-Z.: Interferon lambda inhibits HIV-1 infection of macrophages. J. Virol. 83:3834-3842, 2009.
20231901 Ye, L., Wang, X., Metzger, D.S., Riedel, E., Montaner, L.J., Ho, W-Z.: Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users. PLoS One 5(3):e9602, 2010.
20636339 Zhou, Y., Wang, X., Liu, M., Hu, Q., Song, L., Ye, L., Zhou, D., Ho, W-Z.:
A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages. Immunology. 2010 Jul 16. [Epub ahead of print]
20646875 Ye, L., Wang, S., Wang, X., Zhou, Y., Li, J., Persidsky, Y., Ho, W-Z.: Alcohol impairs interferon signaling and enhances full cycle hepatitis C virus JFH-1 infection of human hepatocytes. Drug Alcohol Depend. 2010 Jun 18. [Epub ahead of print]
20878770 Li J, Hu S, Zhou L, Ye L, Wang X, Ho J, Ho W. Interferon lambda inhibits herpes simplex virus type I infection of human astrocytes and neurons. Glia. 2011 Jan; 59(1):58-67. doi: 10.1002/glia.21076. Epub 2010 Sep 27.
21040279 Liu JP, Ye L, Wang X, Li JL, Ho W-Z. Cyclosporin A inhibits hepatitis C virus replication and restores interferon-alpha expression in hepatocytes. Transpl Infect Dis. 2010 Oct 7. doi: 10.1111/j.1399-3062.2010.00556.x. [Epub ahead of print]
20938809 Zhang J, Ye YQ, Wang Y, Mo PZ, Xian QY, Rao Y, Bao R, Dai M, Liu JY, Guo M, Wang X, Huang ZX, Sun LH, Tang ZJ, Ho W-Z. M. tuberculosis H37Rv Infection of Chinese Rhesus Macaques. J Neuroimmune Pharmacol. 2010 Oct 12. [Epub ahead of print]
21056582 Wang X, Ho W-Z. Drugs of abuse and HIV infection/replication: Implications for mother-fetus transmission. Life Sci. 2010 Nov 4. [Epub ahead of print]
21959967 Dai M, Liu J, Chen DE, Rao Y, Tang ZJ, Ho W-Z, Dong CY.：Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice. Cancer Gene Ther. 2012 Feb; 19:77-83. doi: 10.1038/cgt.2011.65. Epub 2011 Sep 30.
22057682 Li J, Ye L, Wang X, Hu S, Ho W-Z: Induction of interferon-λ contributes to toll-like receptor 3-mediated herpes simplex virus type 1 inhibition in astrocytes. J Neurosci Res. 2012 Feb;90:399-406. doi: 10.1002/jnr.22758. Epub 2011 Nov 4.
21940748 Ye L, Wang X, Li J, Liu J, Ramirez SH, Wu J, Ho W-Z: Tetherin has negligible activity in restricting hepatitis C virus in hepatocytes. Innate Immun. 2011 Sep 22. [Epub ahead of print]
21755286 Wang X, Zhang T, Ho W-Z: Opioids and HIV/HCV infection. J Neuroimmune Pharmacol. 2011 Dec; 6:477-89. Epub 2011 Jul 14.
21499846 Zhou L, Li J, Wang X, Ye L, Hou W, Ho J, Li H, Ho W-Z: IL-29/IL-28A suppress HSV-1 infection of human NT2-N neurons. J Neurovirol. 2011 Jun; 17:212-9. Epub 2011 Apr 16.
21324129 Li J, Ye L, Cook DR, Wang X, Liu J, Kolson DL, Persidsky Y, Ho W-Z:
21224041 Wang X, Ye L, Zhou Y, Liu MQ, Zhou DJ, Ho W-Z: Inhibition of anti-HIV microRNA expression: a mechanism for opioid-mediated enhancement of HIV infection of monocytes. Am J Pathol. 2011 Jan;178:41-7. Epub 2010 Dec 23.
21397004 Persidsky Y, Ho W, Ramirez SH, Potula R, Abood ME, Unterwald E, Tuma R: HIV-1 infection and alcohol abuse: neurocognitive impairment, mechanisms of neurodegeneration and therapeutic interventions. Brain Behav Immun. 2011 Jun; 25 Suppl 1:S61-70. Epub 2011 Mar 21. Review.
21749375 Cook DR, Gleichman AJ, Cross SA, Doshi S, Ho W, Jordan-Sciutto KL, Lynch DR, Kolson DL.: NMDA receptor modulation by the neuropeptide apelin: implications for excitotoxic injury. J Neurochem. 2011 Sep;118(6):1113-23. doi: 10.1111/j.1471-4159.2011.07383.x. Epub 2011 Aug 8.
21940748 Tetherin has negligible activity in restricting hepatitis C virus in hepatocytes. Ye L, Wang X, Li J, Liu J, Ramirez SH, Wu J, Ho W.
Innate Immun. 2012; 18(3):398-405. Epub 2011 Sep 22.
22359571 Morphine suppresses IFN signaling pathway and enhances AIDS virus infection. Wang Y, Wang X, Ye L, Li J, Song L, Fulambarkar N, Ho W.
PLoS One. 2012; 7(2):e31167. Epub 2012 Feb 16.
22558263 IFN-λ3 inhibits HIV infection of macrophages through the JAK-STAT pathway. Liu MQ, Zhou DJ, Wang X, Zhou W, Ye L, Li JL, Wang YZ, Ho WZ.
PLoS One. 2012; 7(4):e35902. Epub 2012 Apr 27.
22591364 Modulation of Intracellular Restriction Factors Contributes to Methamphetamine-mediated Enhancement of Acquired Immune Deficiency Syndrome Virus Infection of Macrophages. Wang X, Wang Y, Ye L, Li J, Zhou Y, Sakarcan S, Ho W. Curr HIV Res. 2012 May 11. [Epub ahead of print]
22591692 CD56+ T cells inhibit HIV-1 infection of macrophages. Hou W, Ye L, Ho WZ. J Leukoc Biol. 2012 May 16. [Epub ahead of print]
22728816 Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells. Ye L, Li J, Zhang T, Wang X, Wang Y, Zhou Y, Liu J, Parekh HK, Ho W. Virus Res. 2012 Jun 21. [Epub ahead of print]
22768975 Li J, Ye L, Wang X, Liu J, Wang Y, Zhou Y, Ho W. (-)-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells. J Neuroinflammation. 2012 Jul 6; 9:161.
23035017 Zhou Y, Guo M, Wang X, Li J, Wang Y, Ye L, Dai M, Zhou L, Persidsky Y, Ho W, TLR3 activation efficiency by high or low molecular mass poly I:C. Innate Immun : 2012 Oct 3
23060457 Wang Y, Ye L, Wang X, Li J, Song L, Ho W. Retinoic acid inducible gene-I (RIG-I) signaling of hepatic stellate cells inhibits hepatitis C virus replication in hepatocytes. Innate Immun. 2012 Oct 11. [Epub ahead of print]
23401273 Li J, Wang Y, Wang X, Ye L, Zhou Y, Persidsky Y, Ho W, Immune activation of human brain microvascular endothelial cells inhibits HIV replication in macrophages. Blood: 2013 Feb 12