Wenzhe Ho, MD, MPH
Dr. Ho’s laboratory is using multidisciplinary approaches to understand virus-host interactions and the basic mechanisms that control virus replication and strategies for enhancing the innate immunity against viral infections, particularly human immunodeficiency virus (HIV) and hepatitis C virus (HCV, a major etiology of liver disease). Working closely with drug abusing populations in the regions of Philadelphia and China, the Ho laboratory is also investigating whether drugs of abuse such as heroin and methamphetamine have a cofactor role in promoting HIV and/or HCV diseases. The work in the Ho laboratory is focused on:
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 to the Ho laboratory is how HIV /HCV escape from host defense mechanisms, resulting in chronic diseases. Studies in the Ho laboratory have demonstrated that IFNs (IFN-alpha, IFN-gamma and IFN-lamda), through triggering intracellular innate antiviral mechanisms, inhibit HIV or HCV replication in human immune and hepatic cells, respectively. These studies are focused on defining the intracellular cellular factors that control HIV or HCV replication in the target cells. Through this work, the Ho laboratory has recently revealed that the newly identified IFN family member, IFN-lamda, and several cellular anti-HIV miRNAs have a key role in protecting monocytes and macrophages from HIV infection. Current projects involved in determining whether host innate immune pathways (such as toll-like receptor, -mediated recognition of viral infections) are critical in control of viral replication and protection of host cells (human immune, hepatocytes and neurons). To study whether the viruses or viral proteins impair the intracellular immune pathway is also a focus of the current research. These studies shall contribute to our basic understanding of host innate immune processes against HIV and/or HCV infections, and provide crucial information for the design and development of innate immunity-based treatment for patients infected with HIV and/or HCV.
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 and methamphetamine) 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, studies in the Ho laboratory have shown that drugs of abuse such as opioids and METH impair antiviral functions of host innate immune cells (natural killer cells and CD56 T natural cells) and facilitate HIV or HIV infection/replication. Current research in the Ho laboratory is investigating the specific effects of opioids such as heroin and morphine on type 1 IFN-mediated intracellular immunity that control HIV or HCV infection and replication. In addition, to determine whether drugs of abuse (opioids and METH) and/or HIV impair the innate immunity in human neurons and compromise the efficacy of HIV treatment (HAART) is also a focus of Dr. Ho’s research.
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 recognize and initiate local and effective innate immune responses against pathogens, which is vital for the CNS protection. It is now known that the CNS cells (neurons, microglia and astrocytes) are the targets for several important viruses such as HIV and herpes simplex virus (HSV). Thus, to determine the mechanisms involved in the regulation of innate immunity within the CNS cells, particularly neurons, is of importance. The recent studies by others and Dr Ho’s laboratory have demonstrated that resident CNS cells including human neurons express several toll-like receptors (TLRs), the sensors of pathogen invasion and triggers for innate immunity activation. The researchers in the Ho laboratory showed that the activation of TLRs or treatment with IFN-lamda, a newly identified member of IFN family, could protect human neurons from viral infections such as herpes simplex virus type 1 (HSV-1). Current research in the Ho laboratory is to identify and determine the role of antiviral cellular factors and mechanisms involved in the protection of the CNS cells from infection/injury caused by viruses or virus-mediated products.