Department of Pathology

What We Do | Research | Selected Publications | Lab Members

« What We Do

We work with rabies and rabies virus. Rabies is a viral disease that affects the central nervous system of mammals, and death usually occurs within days of the onset of symptoms. Rabies is one of the ancient diseases and its history can be traced back to 5000 year ago. Rabies still presents a public health threat today despite extensive research and development in the past one hundred years. Around the globe, more than 70,000 people succumb to rabies every year and millions seek post-exposure treatment due to bites by rabid and suspected rabid animals. Our research focuses on the investigation of the mechanisms by which rabies virus causes neurological diseases and by which rabies virus is attenuated. Since rabies is an infectious disease and a zoonosis, our research efforts have important implications in infectious diseases, neuroscience, and public health.

There are three areas of research conducted in Dr. Fu's laboratory: pathogenesis of neurotropic viruses; virus epidemiology and evolution; and development of novel anti-viral vaccines and therapeutics. The viruses we are working with include rabies, hantavirus, influenza virus, respiratory syncytial virus, and metapneumovirus.

« Research

Rabies is one of the most important zoonotic infections and still causes more than 70,000 human deaths each year. Most of the human rabies cases occur in Asia and Africa where dog rabies is prevalent. In the United States, dog rabies has almost been eliminated through massive vaccination during the past 6 decades. However, bat (particularly the silver-haired bats) rabies has emerged to be responsible for most of the human rabies cases in the past 20 years. Once clinical signs develop, rabies is almost always fatal. Despite the lethality of rabies, only mild inflammation and little neuronal destruction were observed in the CNS of rabies patients. On the other hand, laboratory-attenuated RV induces extensive inflammation and neuronal degeneration in experimentally infected animals. To understand the mechanism of virus attenuation, we have investigated the induction of innate immunity by virulent and attenuated rabies viruses. It has been found that laboratory-attenuated RV activates innate immunity and induces extensive inflammation, apoptosis, and neuronal degeneration in the CNS; however, wt RV caused little to no inflammation or neuronal damage. The induction of innate immunity has been confirmed when other laboratory-attenuated viruses were used to infect mice or neuronal cells. Induced innate immune response genes include inflammatory chemokines (including RANTES, MIP-1a, IP-10) and cytokines (IL-6, IL-1β, and TNF-α), IFN and IFN-related genes (IFN-a/b, STAT1), as well as Toll-like receptors (TLR). These observations led us to hypothesize that laboratory-attenuated RV is a potent inducer of host innate immunity, which might be an important mechanism of RV attenuation. The laboratory is currently investigating the roles of chemokines in rabies pathogenesis and virus attenuation.

The expression of chemokines, particularly MIP-1a, Rantes, and IP-10, correlates with the infiltration of inflammatory cells into the CNS and the enhancement of blood-brain-barrier (BBB) permeability in mice infected with attenuated RV. Enhancement of BBB permeability has been proposed to play an important role in allowing immune effectors to cross the BBB and enter the CNS. We have found that the induction of chemokine expression correlates with the enhancement of BBB permeability, suggesting that chemokine expression may be responsible to the changes in BBB permeability.

Another important project derived from above studies is to develop live-avirulent rabies virus vaccines by cloning and expressing chemokines in rabies virus genome. Up-to-date, MIP-1a, Rantes, and IP-10 have each been incorporated into rabies virus genome. It was found that recombinant rabies virus expressing MIP-1a was further attenuated and does not induce any disease in mice after intracerebral infection. Furthermore this recombinant rabies virus induces higher levels of virus neutralizing antibodies and provides better protection than parental virus. These data indicate that recombinant rabies virus expressing innate immune molecules has the potential to be developed as live-avirulent rabies virus vaccines.

In collaboration with Dr. Zhang in China CDC, we are investigating the epidemiology of rabies virus and hantavirus epidemiology and virus evolution in China. We have found that rabies viruses circulating in China for the past 10 years may present a new group of rabies viruses that are distinguishable from those in terrestrial animals around the world. In addition, research with hantavirus epidemiology has detected PUUV virus in China and our studies shed light on the evolution of hantaviruses in China and around the world.

In collaboration with Dr. Ralph Tripp here at the University of China, we are investigating how respiratory viruses (respiratory syncytial virus, metapneumovirus, and influenza virus) persist in the lung. Our findings indicate that some of these viruses can invade into the nervous fibers during clinical latency period. These viruses can be reactivated after treatment with glucocorticoid. Our laboratory is part of the NIAID Center of Excellence for Influenza Research and Surveillance.

Last Updated March 07, 2009.

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Dr. Fu's Lab

Department of Pathology
College of Veterinary Medicine
The University of Georgia
Athens, GA 30602-7388

(From left to right) In front: Xuexing Zheng, Yongjun (Vincet) Wen, and Hualei (Raymond) Wang.
In back: Fazal Mahmood, Xuefeng Niu, Zhen F. Fu, Joe Fang, Sarah Lackay, and Guoqing (Michael) Zhang.

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Zhen Fang Fu, DVM, PhD

Selected Publications

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Dr. Fu's research is supported by funding from National Institutes of Health (AI51560 and HHSN266200700006C).