Office of China Programs

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China Development Grant - H.I.V. Research

Yong-Hui Zheng, Ph.D. and Walter Esselman Ph.D.

Department of Microbiology and Molecular Genetics:

According to the World Health Organization (WHO), infectious diseases are the second leading cause of death throughout the world. Compared to the other infectious agents, certain viruses have become the most dangerous pathogens and virus-associated infection represents the major threat to public health. The human immunodeficiency virus type 1 (HIV) has become one of the most notorious pestilences in history. This virus has infected 40 million people and killed over half of them in last twenty-five years. In addition, new types of viruses are emerging to endanger human beings due to the quick evolution of their genomes so that they can jump from animals to humans. This situation has been best exemplified by the recent pandemic of the severe acute respiratory syndrome (SARS) caused by a corona virus. In addition, the explosion of the new Avian Influenza Virus stain H5N1 in chickens and birds not only caused 92 deaths in humans, but also implicated a new potential pandemic threat to humans. Renewed and new efforts are required to improve our capacity to respond to these emerging and re-emerging infectious diseases.

My lab was established in 2005 in the Department of Microbiology and Molecular Genetics. Our major focus is to develop new anti-viral agents to block and cure viral infections. Compared to classical strategies, we are more interested in the discovery of drugs that can potentially improve the power of our immunity that ordinarily defends us from these viral invasions. One of the reasons why HIV-1 is so invasive in humans is that this virus can effectively inactivate host defense genes that block its replication. Thus, we are trying to develop agents that block the inactivation of defensive proteins by the virus. We believe this design has tremendous advantages compared to those that directly block the replication of the virus. Accordingly, we have developed a system that can screen synthesized chemical compounds that can protect defensive antiviral proteins, resulting in eventual blockade of HIV replication. In addition, the methods we propose will also have utility in the development of new drugs for SARS and avian influenza.

China is now under a high burden of emerging viral infections. While the memory for the 2003 SARS pandemic is still with us, the new H5N1 influenza has emerged in Asia. Not only are human nutrition and the huge poultry industry threatened, but also it raises serious public health concerns because this virus can be transmitted from chickens to humans. So far, 12 infections and 8 deaths of humans have been reported in China. Moreover, HIV infection is believed to be another serious problem in this country. In 2003, following a joint survey with WHO and UNAIDS, the Chinese government estimated there were around 840,000 HIV infected people in China, including about 80,000 AIDS patients. This did not include those who had already died. If HIV/AIDS prevention is not made a priority in China, the country will be facing HIV epidemics that will be difficult to control.

The objective for this proposal is to request travel funds form MSU to develop new exchange and cooperative research programs between the Department of Microbiology and Molecular Genetics and a research institute in China in the field of infectious diseases. In particular, we will take the resources and new technology developed in the department to partner with and complement our Chinese partners to develop new therapeutics for these viral diseases. Our activity shall definitely promote economic development and cooperation between China and the State of Michigan. Thus, the performance of this project will be divided into three stages.

First, Dr. Esselman, the Chair of the department, and I will visit three renowned research institutions in China: Harbin Veterinary Research Institute (HVRI), associated with the Chinese Academy of Agricultural Sciences; Jilin University (JLU), associated with the Ministry of Education; and Kuming Institute of Zoology (KIZ), associated with the Chinese Academy of Sciences. HVRI is the only institute hosting the national Animal Influenza Center. It has first isolated the H5N1 influenza strain from birds and chickens and has been specified as the only reference lab for the avian influenza by the World Organization for Animal Health (OlE). More recently, it has developed both inactivated and recombinant vaccines that have been widely used in animals. The JLU is distinguished by innovative research and scholarship across the wide range of disciplines. It has now the highest enrollment and is an important national training base for nurturing professionals in various disciplines. Recently, it established a Center For HIV Vaccine Development under the College of Life Science. It has developed a DNA vaccine that is the only HIV vaccine candidate under clinical trials in the country. Finally, the country’s only primate center was established at KIZ, which has been equipped with a state of the art BL-3 animal facility. It has the capacity to do in vivo experiments using SIV or SHIV-infected rhesus monkeys as a model. In addition, it has access to a natural compound library for drug screening. We will meet Professor Guang-Zhi Tong’s group at HVRI, Professor Wei Kong’s group at JLU, and Professor Yong-Tang Zheng’s group at KIZ during this trip. We will review our research achievements in blocking viral infection and we will plan areas for future collaboration. Of the three institutions we expect to identify one or more that will collaborate in a joint program on HIV and/or influenza research with Michigan State University.

In the second phase, we will invite our Chinese partners to visit MSU and our department. The purpose for this visit is to give our collaborators a chance to evaluate our research facilities and interact with a variety of faculty members. In addition, we will demonstrate our several state of the art core and animal facilities, which should be very attractive to our collaborators. During this visit, collaborative research topics will be finalized and applications for funding from both US and China will be planned for continued support of these collaborations.

In the third phase, we will jointly apply for financial support from different funding agencies. Such international collaboration requires funds to cover the costs for scholar exchange, reagents, and travels. Our application will target agencies in both China and the US, and each party will take responsibility in their own country for their respective applications. Fortunately, many funding agencies have a mechanism to support this type of collaboration. For example, in China, funds are available from Ministry of Health, Ministry of Science and Technology, Ministry of Agriculture, and others. In the US, the National Institutes of Health, Howard Hughes Medical Institute, Bill & Melinda Gates foundation, and others provide many opportunities.