Research Interests

Dr. Meng's lab studies the molecular mechanisms of viral replication and pathogenesis and developing vaccines against emerging, re-emerging and zoonotic viral diseases. Viruses currently being studied in Dr. Meng's lab include the hepatitis E virus (human, swine and avian HEVs), porcine circoviruses, and porcine reproductive and respiratory syndrome virus.

Dr. Meng's research projects are funded by various federal grant agencies, non-profit organizations and private sectors including:
**National Institutes of Health (AI050611; AI046505; AI01653; AI065546; AI74667; RR021819)
**USDA-NRI Competitive Grant Programs (NRI 2002-35204-12531; NRI2004-35204-14213)
**American Cancer Society (IRG-99-225-01)
**National Pork Board
**Fort Dodge Animal Health Inc./Wyeth Inc Animal Health
**Boehringer Ingelheim Vetmedica Inc.
**Genentech Inc.
**Navigant Biotechnologies Inc.

I: Hepatitis E virus (HEV)

HEV, the causative agent of human hepatitis E, belongs to the genus Hepevirus, family Hepeviridae. Hepatitis E is an important public health disease in many developing countries, and sporadic cases of hepatitis E have also been reported in industrialized countries including the United States. A vaccine against HEV is not yet available. In 1997, our group discovered and characterized the first animal strain of HEV, swine HEV, from a pig in the United States. We showed that swine HEV can cross species barriers and infect non-human primates. In 2001, our group discovered yet another animal strain of HEV, avian HEV, from chickens with Hepatitis-Splenomegaly syndrome in the United States. Avian HEV can also cross species barriers and infect turkeys. Hepatitis E is now a recognized zoonotic disease and pigs (and maybe other animal species) are reservoirs. Currently, our research efforts focus on the molecular mechanisms of pathogenesis and replication, cross-species infection and zoonosis, natural history, and vaccine development. We are now studying the structural and functional relationship of HEV genes, and understanding the molecular mechanism of HEV cross species infection by using various HEV reverse genetic systems and chimeric viruses among human, swine and avian HEVs and by using swine and chickens as animal model systems.

Representative publications:

Meng X.J., R.H. Purcell, P.G. Halbur, J.R. Lehman, D.M. Webb, T.S. Tsareva, J.S. Haynes, B.J. Thacker, and S.U. Emerson (1997). A novel virus in swine is closely related to the human hepatitis E virus. Proceedings of the National Academy of Sciences USA 94:9860-9865. (Abstract)

Meng X.J., P.G. Halbur, M. Shapiro, S. Govindarajan, J.D. Bruna, I. K. Mushahwar, R.H. Purcell, and S.U. Emerson (1998). Genetic and experimental evidence for cross-species infection by the swine hepatitis E virus. Journal of Virology. 72:9714-9721. (Abstract)

Kabrane-Lazizi, Y., X.J. Meng, R.H. Purcell, and S.U. Emerson. Evidence that the genomic RNA of hepatitis E virus is capped (1999). Journal of Virology. 73:8848-8850. (Abstract)

Emerson SU, Zhang M, Meng X.J., St. Clair M, Nguyen H, Huang Y, and Purcell RH (2001). Recombinant hepatitis E virus genomes infectious for primates: importance of capping and discovery of a cis-reactive element. Proceedings of the National Academy of Sciences USA 98:15270-15275. (Abstract)

Haqshenas, G., H.L. Shivaprasad, P. Woolcock, D. Read, and X.J. Meng (2001). Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-spleenomegaly syndrome. Journal of General Virology. 82:2449-2462. (Abstract)

Meng X.J. (2003). Swine hepatitis E virus: cross-species infection and risk in xenotransplantation. Current Topics in Microbiology and Immunology. 278:185-216. (Abstract)

Huang Y.W., G. Haqshenas, C. Kasorndorkbua, P.G. Halbur, S.U. Emerson, and X.J. Meng (2005). Capped RNA transcripts of full-length cDNA clones of swine hepatitis E virus are replication-competent when transfected into Huh7 cells and infectious when intrahepatically inoculated into pigs. Journal of Virology. 79:1552-1558. (Abstract).

Billam P., F.F. Huang, Z.F. Sun, F.W. Pierson, R.B. Duncan, F. Elvinger, D.K. Guenette, T.E. Toth, and X.J. Meng (2005). Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens. Journal of Virology. 79:3429-3437. (Abstract).

Huang YW, Oprissnig T, Halbur PG, and Meng XJ (2007). Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo. Journal of Virology. 81:3018-3026. (Abstract).

II: Porcine Circovirus (PCV)

Type-2 porcine circovirus (PCV2), an emerging virus in pigs, is the primary causative agent of postweaning multisystemic wasting syndrome (PMWS) (now known as "Porcine Circovirus-Associated Diseases or PCVAD") in pigs worldwide including the United States. 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/PCVAD currently has a serious economic impact on the global swine industry. We have recently developed the first USDA fully-licensed vaccine, Suvaxyn® PCV2 One Dose™, to combat PCV2 infection and PCVAD, and this vaccine is being marketed by Wyeth/Ft Dodge Animal Health Inc. Our current research efforts focus on understanding of the molecular basis of PCV2 pathogenesis and replication and development of a second-generation vaccine against PCV2 and PCVAD.

Representative publications:

Fenaux, M., P.G. Halbur, G. Haqshenas, R. Royer, P. Nawagitgul, M. Gill, T.E. Toth, and X.J. Meng (2002). The cloned genomic DNA of the type-2 porcine circovirus (PCV-2) is infectious when injected into the liver and lymph nodes of SPF pigs: characterization of clinical course, virus distribution and pathological lesions. Journal of Virology. 76:541-551. (Abstract).

Fenaux M, Opriessnig T, Halbur PG, and Meng XJ (2003). Immunogenicity and pathogenicity of chimeric infectious DNA clones of pathogenic porcine circovirus type 2 (PCV2) and nonpathogenic PCV1 in weanling pigs. Journal of Virology. 77:11232-11243. (Abstract).

Lekcharoensuk P, Morozov I, Paul PS, Thangthumniyom N, Wajjawalku W, and Meng XJ (2004). Epitope mapping of the major capsid protein of type 2 porcine circovirus (PCV2) by using chimeric PCV1 and PCV2. Journal of Virology. 78:8135-8145 (Abstract).

Fenaux M, Opriessnig T, Halbur PG, Elvinger F, and Meng XJ (2004). A chimeric porcine circovirus (PCV) with the immunogenic capsid gene of the pathogenic PCV type 2 (PCV2) cloned into the genomic backbone of the nonpathogenic PCV1 induces protective immunity against PCV2 infection in pigs. Journal of Virology. 78:6297-6303. (Abstract).

Fenaux M, Opriessnig T, Halbur PG, Elvinger F, Meng XJ. 2004. Two amino acid mutations in the capsid protein of type 2 porcine circovirus (PCV2) enhanced PCV2 replication in vitro and attenuated the virus in vivo. Journal of Virology. 78:13440-13446. (Abstract).

McKeown NE, T. Opriessnig, P. Thomas, D. K. Guenette, F. Elvinger, M. Fenaux, P.G. Halbur, and X.J. Meng (2005). Effects of type 2 porcine circovirus (PCV2) maternal antibodies on experimental infection of piglets with PCV2. Clinical and Diagnostic Laboratory Immunology. 12:1347-1351. (Abstract).

Opriessnig T, N.E. McKeown, E. Zhou, X.J. Meng, P.G. Halbur (2006). Genetic and experimental comparison of porcine circovirus type 2 (PCV2) isolates from cases with and without PCV2-associated lesions provides evidence for differences in virulence. Journal of General Virology. 87:2923-2932. (Abstract).

Gillespie J, N.M. Juhan, J. DiCristina, K.F. Key, S. Ramamoorthy, and X.J. Meng ( 2008). A genetically-engineered chimeric vaccine against porcine circovirus type 2 (PCV2) is genetically stable in vitro and in vivo. Vaccine. In Press, 2008 Jun 6. [Epub ahead of print] (Abstract)

III: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

Porcine reproductive and respiratory syndrome (PRRS), was first recognized in 1987 in the United States. The disease was characterized by severe reproductive failure in sows and respiratory diseases in young pigs. 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. Despite intensive research over the last decade, PRRS remains difficult to control. Our current research efforts focus on understanding the molecular mechanisms of PRRSV pathogenesis and replication by using PRRSV reverse genetics system, and developing safer and more effective vaccines and antivirals against PRRSV.

Representative publications:

Key KF, Dicristina J, Gillespie J, Guenette DK, Meng XJ (2007). Abstract Direct inoculation of RNA transcripts from an infectious cDNA clone of porcine reproductive and respiratory syndrome virus (PRRSV) into the lymph nodes and tonsils of pigs initiates PRRSV infection in vivo. Archieves of Virology 2007 Mar 15; [Epub ahead of print] (Abstract).

Key, K.F., D.K. Guenette, K.J. Yoon, P.G. Halbur, E.M. Vaughn, M. Roof, T.E. Toth, and X.J. Meng (2003). Development of a heteroduplex mobility assay to identify field isolates of porcine reproductive and respiratory syndrome virus with nucleotide sequences closely related to those of modified live-attenuated vaccines. Journal of Clinical Microbiology. 41: 2433 -2439. (Abstract)

Opriessnig T., P.G. Halbur, K.J. Yoon, R. Pogranichniy, E. Vaughn, K. Harmon, R.Evans, K.F. Key, F. Pallares, P. Thomas, and X.J. Meng (2002). Comparison of molecular and biological characteristics of a modified live PRRSV vaccine (RespPRRS/Repro™), the parent strain of the vaccine (ATCC VR2332), ATCC VR2385, and two recent field isolates of PRRSV. Journal of Virology. 76:11837-11844. (Abstract)

Meng X.J., P.S. Paul, I. Morozov, and P.G. Halbur (1996). A nested set of six or seven subgenomic mRNAs is formed in cells infected with different isolates of porcine reproductive and respiratory syndrome virus. Journal of General Virology. 77:1265-1270. (Abstract)

Meng X.J., P.S. Paul, P.G. Halbur, and I. Morozov (1995). Sequence comparison of open reading frames 2 to 5 of low and high virulence U.S. isolates of porcine reproductive and respiratory syndrome viruses. Journal of General Virology. 76:3181-3188. (Abstract)

Meng X.J., P.S. Paul, and P.G. Halbur (1994). Molecular cloning and nucleotide sequencing of the 3' terminal genomic RNA of porcine reproductive and respiratory syndrome virus. Journal of General Virology. 75:1795-1801. (Abstract).

IV: Other Viruses

Dr. Meng is also interested in studying other recent emerging viruses such as SARS-coronavirus and the porcine TT virus.

Representative publications:

Sun ZF, and Meng XJ (2004). Antigenic cross-reactivity between the nucleocapsid protein of severe acute respiratory syndrome (SARS) coronavirus and polyclonal antisera of antigenic group I animal coronaviruses: implication for SARS diagnosis. Journal of Clinical Microbiology. 42:2351-2352. (Abstract)

McKeown NE, Fenaux M, Halbur PG, and Meng XJ (2004). Molecular characterization of porcine TT virus, an orphan virus, in pigs from six different countries. Veterinary Microbiology. 104:113-117. (Abstract)