I studied Medicine in the early 1980s and received my medical degree in 1985 from Binzhou Medical College, China. Subsequently I enrolled in the Graduate School of Wuhan University School of Medicine (formerly Hubei Medical College) where I studied the role of human papillomaviruses and herpes simplex virus in the development of cervical carcinoma, and received my M.S. in 1988. For the next three years, I moved to Shandong Academy of Medical Sciences and continued to work on human papillomavirus and herpes simplex virus as a Research Associate.

“The ultimate goals for most of my research projects are to develop vaccines and other preventive and control measures against important viral diseases of man and other animals.”

In early 1991, I came to Iowa State University in Ames, where I studied an emerging virus known as porcine reproductive and respiratory syndrome virus (PRRSV) in the laboratory of Prem S. Paul. After receiving my Ph.D. from Iowa State in 1995, I worked as a John E. Fogarty visiting scientist and subsequently as a senior staff scientist in the laboratories of Suzanne U. Emerson and Robert H. Purcell at the National Institutes of Health in Bethesda, Maryland, where I studied the hepatitis E virus. Since 1999, I have been a faculty member at the Virginia Polytechnic Institute and State University in Blacksburg, Virginia, where I am currently a Professor of Molecular Virology.

I have a keen interest in comparative and translational medicine, and my main research focus has been in the field of comparative viral pathogenesis with emphasis on emerging, re-emerging, and zoonotic viral diseases that are important to both human and veterinary public health. The ultimate goals for most of my research projects are to develop vaccines and other preventive and control measures against important viral diseases of man and other animals.

What drew my interest to this particular area? I have been trained in both medical and veterinary sciences; therefore I feel that, by conducting biomedical research in the field of comparative viral pathogenesis, I can contribute in a meaningful way to both human and veterinary medicine. Historically, comparative medicine and animal models have been instrumental in understanding the pathogenesis and mechanism of many human diseases.

Many important scientific discoveries are serendipitous, and this study certainly fits in this category. This paper describes the initial discovery and characterization of the swine hepatitis E virus (swine HEV), which now is recognized as a zoonotic pathogen.

While I was in the Laboratory of Infectious Diseases’s Hepatitis Virus Section and Molecular Hepatitis Section headed by Robert H. Purcell and Suzanne U. Emerson at NIH, I accidentally found out that the majority of the pigs in the United States had high levels of antibody prevalence to the human HEV. This finding was very puzzling at that time, since hepatitis E was not considered to be endemic in humans in the United States, and thus it was difficult to explain the observed high HEV antibody prevalence in pigs.

Through my old contacts in the veterinary sciences (Joseph Haynes and Patrick Halbur at Iowa State University, and James Lehman and Dale Webb from the Illinois Department of Agriculture), we set up this prospective study with an aim to identify this unknown agent in pigs that antigenically reacts to the human HEV. This study led to the discovery of swine HEV, a ubiquitous virus in pigs that can infect humans.

We demonstrated in this study that the majority of the pigs in swine herds in the United States were infected by swine HEV, and that, most importantly, swine HEV is genetically and antigenically closely related to its human counterpart, with more than 90% amino acid sequence identity, thus raising a public health concern of human infections by swine HEV.

The findings from this study have essentially revolutionized the way scientists and physicians used to think about this important human disease, as hepatitis E is now a recognized zoonotic disease, and pigs (and perhaps other species) are animal reservoirs.

Since our initial 1997 PNAS report on the discovery of swine HEV, we have subsequently published more than 40 peer-reviewed papers on HEV and studied various aspects of the virus, including molecular biology, pathogenesis, epidemiology, vaccine development, and public health.

Soon after the 1997 PNAS publication, I proposed a then-controversial hypothesis that pigs are animal reservoirs for HEV and hepatitis E is a zoonotic disease. To prove the hypothesis, we have since demonstrated the ability of cross-species infection by HEV: swine HEV-infected non-human primates, and human HEV-infected pigs. We also showed that swine veterinarians and other pig workers in the United States are at increased risk of HEV infection. With reports from Japan that people who consumed uncooked or undercooked pig livers from infected pigs developed acute hepatitis E, the HEV zoonosis concept has now been approved and is well accepted in the scientific community.

We have since discovered yet another virus from chickens with Hepatitis-Splenomegaly syndrome in the United States, designated avian hepatitis E virus (avian HEV), and demonstrated that, like swine HEV, avian HEV is also genetically and antigenically similar to human HEV.

We have developed reverse genetic systems for swine HEV and avian HEV, and developed unique convenient animal models (pigs and chickens) to study the replication and pathogenesis of HEV. Using these reverse genetic systems, we have studied the structural and functional relationship of HEV genes. Using swine and avian HEV and the animal model systems, we have since learned a great deal about the biology and pathogenesis of HEV.

Currently we are working on understanding the molecular mechanisms of HEV cross-species infection and virulence, and hoping that in the near future we can develop a vaccine against this important human pathogen.

Over the years during my career, I have studied and published research papers for numerous viruses including human papillomavirus, herpes simplex virus, human cytomegalovirus, swine encephalomyocarditis virus, porcine reproductive and respiratory syndrome virus, porcine circovirus, and hepatitis E virus (human, swine, and avian).

Hepatitis E virus (human, swine, and avian) is still my main research focus; however, my lab studies multiple virus systems. Besides HEV, my current research also focuses on two other emerging viruses: porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus.

PCV2, an emerging virus in pigs, is the primary causative agent of postweaning multisystemic wasting syndrome (PMWS) in pigs worldwide. The disease occurs in high-health swine herds as a low-morbidity but high-case-fatality disease of 5- to 16-week-old pigs. PMWS and porcine circovirus-associated diseases (PCVAD) currently pose a serious economic impact on the global swine industry, making PCV2 one of the most economically important swine pathogens. We have been studying PCV2 since 1999, and have published more than 16 peer-reviewed papers on various aspects of PCV2.

Our research recently led to the development of a chimeric PCV1-2 virus that is attenuated in pigs but induces protective immunity against PCV2 challenge. Based upon this PCV1-2 chimeric virus, we developed the first USDA fully licensed vaccine, Suvaxyn® PCV2 One Dose™, which is marketed by Wyeth Inc. and Fort Dodge Animal Health Inc., to combat PCV2 infection and PCVAD. By using a chimeric virus strategy, we have also mapped the antigenic sites on the capsid protein of PCV2 and identified putative critical amino acid mutations that are important for virulence. Our current research efforts on PCV2 focus on understanding the molecular basis of PCV2 pathogenesis and replication and development of a second-generation vaccine.

PRRS, characterized by severe reproductive failure in sows and respiratory diseases in young pigs, was first recognized in 1987 in the United States. Since its first appearance in 1987, PRRS has been devastating to the global swine industry, causing tremendous economic losses for pork producers. The causative agent of PRRS, porcine reproductive and respiratory syndrome virus (PRRSV), is a single-stranded positive-sense RNA virus in the family of Arteriviridae. Over the years we have studied various aspects of PRRSV including pathogenesis, replication mechanism, vaccine efficacy, and virus evolution, and we have published more than 20 peer-reviewed papers on PRRSV. We were the first group that published the cloning and sequencing of the U.S. strain of PRRSV in a peer-reviewed journal. We did some of the earlier fundamental work on PRRSV genetics including the characterization of the subgenomic mRNA. We demonstrated the existence of vaccine-derived PRRSV isolates that are still pathogenic.

More recently, we developed a unique approach to infect pigs directly via in vivo transfection with RNA transcripts from infectious cDNA clone of PRRSV, and we have used this unique strategy to study PRRSV quasispecies evolution. Our current research efforts focus on understanding the molecular mechanisms of PRRSV pathogenesis, and developing safer and more effective vaccines and antivirals against PRRSV.

As I mentioned before, the ultimate goals for most of my research projects are to develop vaccine and other preventive and control measures against several viral diseases of human and veterinary public health importance. To this end, we have successfully developed a USDA-fully licensed commercial vaccine, Suvaxyn® PCV2 One Dose™, against a deadly veterinary pathogen, PCV2, and its associated diseases.

I hope that, with continuous research in HEV and PRRSV, in the next five to ten years we will be able to develop a candidate vaccine with improved safety and efficacy against PRRSV, and we will be able to efficiently propagate HEV in cell cultures to facilitate the efforts for the development of an attenuated-live vaccine against HEV.

X.J. Meng, M.D., Ph.D.
Professor of Molecular Virology
Department of Biomedical Sciences and Pathobiology
Center for Molecular Medicine and Infectious Diseases
College of Veterinary Medicine
Virginia Polytechnic Institute and State University
Blacksburg, VA, USA