Profile of Xiang-Jin Meng

Trained in both human medical and veterinary sciences, Xiang-Jin Meng has made numerous contributions to the field of comparative viral pathogenesis. His achievements concerning emerging, reemerging, and zoonotic viral diseases include the discovery of swine and avian hepatitis E viruses (HEV) and the invention of a commercial vaccine against porcine circovirus type 2 (PCV2), a common pathogen reported in pigs. For these and other accomplishments, Meng, a University distinguished professor of molecular virology at Virginia–Maryland College of Veterinary Medicine at Virginia Polytechnic Institute and State University (Virginia Tech), was elected a member of the National Academy of Sciences in 2016. Meng’s Inaugural Article reports the establishment of an animal model for chronic HEV, a virus that causes more than 20 million liver infections in humans each year. The chronic hepatitis E model will help test promising antiviral drugs against this infectious agent, which in its zoonotic genotypes can infect several animal species.

Xiang-Jin Meng. Image courtesy of Virginia Tech/Logan Wallace.

Early Years

Meng was born and raised in Gaomi, Shandong Province, China. “My dream college after high school was a chemical engineering school located only about one hour away from where I was born; however, my national college entrance exam score was not good enough to be admitted to this school,” recalls Meng. With the local engineering school scratched off his list of possibilities, Meng applied to Binzhou Medical College, where he was admitted in 1980 as a medical student.

After receiving his medical degree in medicine in 1985, Meng did not wish to practice medicine full time. He traveled to southern China, where he pursued a Master’s degree in microbiology and immunology at Wuhan University College of Medicine (formerly Hubei Medical College). “It was there I began to develop a very strong curiosity about virology, a field that I have since enjoyed working in so much,” Meng says. His graduate advisor and mentor at the college was Yu Sun, an experimental virologist and pathologist who fostered Meng’s research interests.

Upon earning a Master’s degree in 1988, Meng returned to Shandong Province, where he worked as a research fellow for three years at the Shandong Academy of Medical Sciences in Jinan. In 1991 he was admitted to the interdepartmental immunobiology graduate program at Iowa State University’s College of Veterinary Medicine. Prem S. Paul, a veterinary virologist, sparked Meng’s interest in emerging animal viruses of veterinary public health importance.

Discovery of Swine HEV

After receiving his PhD in immunobiology, Meng worked as a visiting scientist in the hepatitis viruses section of the NIH (1995–1998) and then held a senior staff fellow position in the NIH molecular hepatitis section (1998–1999). While in the NIH laboratories of molecular virologist Suzanne U. Emerson and viral epidemiologist and vaccinologist Robert H. Purcell, Meng honed his research skills. “Their influence on me was enormous and clearly reflects what I do today,” Meng says.

As he studied serological data on animals, Meng noticed that the majority of pigs in the United States had high levels of antibodies for human HEV. He says, “I was very puzzled by this because HEV was not thought to be endemic in the US.” Meng, Purcell, Emerson, and their colleagues analyzed serum samples from swine in commercial herds and discovered a virus that is genetically and immunologically related to human HEV. They named the virus “swine HEV” and warned that it was prevalent in pigs in the United States and could be zoonotic (1).

Evidence for HEV Zoonosis

The following year, the researchers inoculated rhesus monkeys and a chimpanzee with swine HEV. All the test animals became infected with the virus (2). Specific pathogen-free pigs were then inoculated with a strain of human HEV that is genetically similar to swine HEV. The pigs became infected with this virus. Meng says, “In this paper, we demonstrated that swine HEV can cross species barriers and infect nonhuman primates—surrogates for people—and, conversely, a genotype 3 strain of human HEV virus can also cross the species barrier and infect pigs.”

The discovery led to a paradigm shift concerning HEV, resulting in intensive research showing that the virus that can be spread through contact with infected animals or via contaminated food or water. Meng analyzed 127 packages of pig livers sold in US grocery stores and found that 14 tested positive for HEV (3). Although the majority of human patients who contract HEV from these and other sources typically recover over time, immunocompromised individuals, particularly solid-organ transplant recipients, are at greater risk of developing chronic HEV infection, which can result in death. According to the World Health Organization, 56,600 individuals on average die from HEV infection every year (4).

Discovery of Avian HEV

In 1999 Meng accepted the position of Assistant Professor of Molecular Virology at Virginia Tech’s Virginia–Maryland College of Veterinary Medicine. An early research project at Virginia Tech was to study hepatitis-splenomegaly syndrome in chickens in the United States. Outbreaks of this once-mysterious disease were first reported in the 1980s in chickens raised for food in many countries. The disease can lower egg production and increase mortality.

Meng and his team analyzed bile samples from chickens with the syndrome and identified the causative agent, which they named “avian HEV.” (5) “Like swine HEV, the avian HEV is also genetically and antigenically related to human hepatitis E virus,” Meng says. “This discovery led to the development of a useful small animal model—chicken—that can mimic certain aspects of the clinical disease of human hepatitis E, since avian HEV infection in chickens is associated with a hepatic disease.”

Vaccine for Porcine Circovirus Type 2

Meng and his colleagues next turned their attention to PCV2, an emerging virus causing high morbidity in pigs between 5 and 16 wk of age. The virus has been reported in pigs worldwide and poses a threat to the global swine industry. Meng and his team created a chimeric virus, PCV1–2, with the capsid gene of the pathogenic PCV2 cloned in the genomic structure of the nonpathogenic PCV1. The chimeric virus was injected into test pigs and induced protective immunity against PCV2 infection (6).

The chimeric vaccine PCV1–2 developed from the study became the seed virus stock for a licensed commercial vaccine, now known as “Fostera PCV,” against PCV2 and its associated diseases. The vaccine has been on the global market since 2006. Meng says, “This vaccine has already saved hundreds of millions of dollars for the global swine industry.”

He additionally led efforts to clone and partially sequence a US strain of porcine reproductive and respiratory syndrome virus (PRRSV) (7), which can spread rapidly in herds. Meng says, “PRRSV is arguably the most economically important swine pathogen in the global swine industry.” The study provided the foundation for future development of vaccines and diagnostic assays for PRRSV. For this achievement and others, Meng received the 2001 and 2007 Pfizer Award for Research Excellence and the 2017 Outstanding Faculty Award from the State Council of Higher Education for Virginia and was elected a fellow of both the American Academy of Microbiology (2012) and the National Academy of Inventors (2014).

Teamwork in and out of the Laboratory

With 17 other colleagues, Meng reported in his Inaugural Article the establishment of a chronic HEV animal model in pigs (8). They used it to demonstrate that active suppression of HEV-specific cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection and outlined future possibilities for the model. Meng says, “This unique animal model will help test promising antiviral drugs against chronic HEV in the future and will also help delineate the underlying mechanism of chronic HEV in immunocompromised individuals.”

A recombinant vaccine against HEV is currently available in China. Meng and his team hope to develop a more affordable vaccine against HEV, such as a modified live-attenuated one. They are also working to develop the next generation of vaccines against PRRSV and PCV2 and have the goal of identifying the host factors and virus genetic elements that are responsible for cross-species infection of HEV.

Meng credits much of his success to his dedicated teams, both in and out of the laboratory. He says, “I am grateful for the great work done by past and present graduate students, postdoctoral fellows, and staff, as well as my collaborators at Virginia Tech and other institutions. I am thankful for the sacrifice and unconditional support from my family, particularly my wife Dr. Wen Li, and my two children, Melissa and Bowen. Throughout my career, I have strongly believed in the importance of team-oriented research, because in this day and age where scientific problems are so complex, it is difficult to work alone and solve such problems.”