January
2008 (originally featured in in-cites.com)
X.J. Meng
Featured Scientist Interview
According to a recent analysis of
Essential Science IndicatorsSM data, the work
of Professor X.J. Meng has entered the top 1% by total
citations in the field of Microbiology, with 31
original articles and review papers published in the
past decade cited a total of 896 times to date.
Professor Meng is also in the top 1% of researchers in
the field of Clinical Medicine. Professor Meng’s
full record in our database includes 68 papers cited a
total of 1,842 times to date, which includes original
articles and review papers from January 1997 to August
2007. Professor Meng is Professor of Molecular Virology
at Virginia Polytechnic Institute and State University
in Blacksburg, Virginia. In the interview below, he
talks about his highly cited research.
Please tell us a little about your research and
educational background.
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.
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.
What do you consider the main focus of your
research, and what drew your interest to this particular area?
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.
Your most-cited paper in our database is the 1997
PNAS article, "A novel virus in swine is closely related to the
human hepatitis E virus." Would you describe the aims and findings of
this work for our readers?
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.
What directions have you taken your work on
HEV since the 1997 paper?
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.
What other viruses have you studied, and what have
you found out about them?
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.
Where do you see this research going in five to
ten years?
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
Meng XJ, et al., "A novel virus in swine is
closely related to the human hepatitis E virus," PNAS
USA 94(18): 9860-5, 2 September 1998. Source:
Essential Science Indicators from
Thomson
Reuters.