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, Torque teno sus virus 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; HHSN272200800962P; OD010430)
**USDA Competitive Grant Programs (NRI 2002-35204-12531; NRI2004-35204-14213; AFRI-2010-03437)
**USDA-Coordinated Agriculture Program (CAP-2008-55620-19132)
**American Cancer Society (IRG-99-225-01)
**National Pork Board
**Pfizer Animal Health Inc./Fort Dodge Animal Health Inc./Wyeth Inc Animal Health
**Boehringer Ingelheim Vetmedica Inc.
**Navigant Biotechnologies Inc.
**USDA National Institute of Food and Agriculture grants (NIFA 2010-034337)
I: Hepatitis E virus (HEV)
HEV, the causative agent of human hepatitis E, belongs to the 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, we 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.
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)
Pudupakam RS, Huang YW, Opriessnig T, Halbur PG, Pierson FW, X.J. Meng (2009). Deletions of the hypervariable region (HVR) in open reading frame 1 of hepatitis E virus do not abolish virus infectivity: evidence for attenuation of HVR deletion mutants in vivo. Journal of Virology. 83:384-395. (Abstract)
Cao D, Y.W. Huang, and X.J. Meng (2010). The nucleotides on the stem-loop RNA structure in the junction region of the hepatitis E virus (HEV) genome are critical for virus replication. Journal of Virology. 84(24):13040–13044. (Abstract)
Córdoba L, Huang YW, Opriessnig T, Harral KK, Beach NM, Finkielstein CV, Emerson SU, Meng XJ (2011). Three amino acid mutations (F51L, T59A, and S390L) in the capsid protein of the hepatitis E virus collectively contribute to virus attenuation. Journal of Virology. 85(11):5338-49. (Abstract)
Pudupakam RS, Kenney SP, Córdoba L, Huang YW, Dryman BA, Leroith T, Pierson FW, Meng XJ (2011). Mutational Analysis of the Hypervariable Region of the Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication. Journal of Virology. 85(19):10031-40. (Abstract)
Kenney SP, Pudupakam RS, Huang YW, Pierson FW, LeRoith T, Meng XJ (2012). The PSAP motif within the ORF3 protein of an avian strain of the hepatitis E virus is not critical for viral infectivity in vivo but plays a role in virus release. Journal of Virology. 86(10):5637-46. (Abstract)
Karpe YA, Meng XJ (2012). Hepatitis E virus replication requires an active ubiquitin-proteasome system. Journal of Virology. 86(10):5948-52. (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, Fostera™ PCV (formerly Suvaxyn® PCV2 One Dose™), to combat PCV2 infection and PCVAD, and this vaccine is being marketed by Pfizer 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.
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).
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. 26:4231-4236. (Abstract)
Beach NM, Juhan NM, Cordoba L, and X.J. Meng (2010). Replacement of the replication factors of porcine circovirus (PCV) type 2 with those of PCV type 1 greatly enhances viral replication in vitro. Journal of Virology. 84(17):8986-8989. (Abstract)
Beach NM, Ramamoorthy S, Opriessnig T, Wu SQ, and X.J. Meng (2010). Novel chimeric porcine circovirus (PCV) with the capsid gene of the emerging PCV2b subtype cloned in the genomic backbone of the non-pathogenic PCV1 is attenuated in vivo and induces protective and cross-protective immunity against PCV2b and PCV2a subtypes in pigs. Vaccine. 29(2):221-232. (Abstract)
Beach NM, Smith SM, Ramamoorthy S, Meng XJ (2011). Chimeric porcine circoviruses (PCV) containing amino acid epitope tags in the C terminus of the capsid gene are infectious and elicit both anti-epitope tag antibodies and anti-PCV type 2 neutralizing antibodies in pigs. Journal of Virology. 85(9):4591-5. (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.
Ni YY, Opriessnig T, Zhou L, Cao D, Huang YW, Halbur PG, Meng XJ (2012). Attenuation of porcine reproductive and respiratory syndrome virus by molecular breeding of the virus envelope genes from genetically divergent strains. Journal of Virology. 2012 Oct 17. [Epub ahead of print]. (Abstract)
Zhou L, Ni YY, Piñeyro P, Sanford BJ, Cossaboom CM, Dryman BA, Huang YW, Cao DJ, Meng XJ (2012). DNA shuffling of the GP3 genes of porcine reproductive and respiratory syndrome virus (PRRSV) produces a chimeric virus with an improved cross-neutralizing ability against a heterologous PRRSV strain. Virology. 434(1):96-109. (Abstract)
Ni YY, Huang YW, Cao D, Opriessnig T, Meng XJ (2011). Establishment of a DNA-launched infectious clone for a highly pneumovirulent strain of type 2 porcine reproductive and respiratory syndrome virus: identification and in vitro and in vivo characterization of a large spontaneous deletion in the nsp2 region. Virus Research. 160(1-2):264-73. (Abstract)
Huang YW, and X.J. Meng (2010). Novel strategies and approaches to develop the next generation of vaccines against porcine reproductive and respiratory syndrome virus (PRRSV). Virus Research. 154(1-2):141-149. (Abstract)
Huang YW, Fang Y, Meng XJ (2009). Identification and characterization of a porcine monocytic cell line supporting porcine reproductive and respiratory syndrome virus (PRRSV) replication and progeny virion production by using an improved DNA-launched PRRSV reverse genetics system. Virus Research. 145(1):1-8. (Abstract)
Huang YW, Dryman BA, Li W, X.J. Meng (2009). Porcine DC-SIGN: Molecular cloning, gene structure, tissue distribution and binding characteristics. Developmental and Comparative Immunology. 33(4):464-480. (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: Torque Teno Sus Virus (TTSuV)
Torque teno sus virus (TTSuV) is an emerging swine virus that has been incriminated in a number of disease conditions in pigs including postweaning multisystemic wasting syndrome (PMWS) and porcine circovirus-associated diseases (PCVAD). Our current research focuses on understanding the mechanisms of pathogenesis, replication and transmission as well as immunogenicity and biology of TTSuVs. The ultimate goal is to develop effective preventive measures against TTSuVs.
Huang YW, Patterson AR, Opriessnig T, Dryman BA, Gallei A, Harrall KK, Vaughn EM, Roof MB, Meng XJ (2012). Rescue of a porcine anellovirus (torque teno sus virus 2) from cloned genomic DNA in pigs. Journal of Virology. 86(11):6042-54. (Abstract)
Huang YW, Harrall KK, Dryman BA, Opriessnig T, Vaughn EM, Roof MB, Meng XJ (2012). Serological profile of torque teno sus virus species 1 (TTSuV1) in pigs and antigenic relationships between two TTSuV1 genotypes (1a and 1b), between two species (TTSuV1 and -2), and between porcine and human anelloviruses. Journal of Virology. 86(19):10628-39. (Abstract)
Huang YW, Dryman BA, Harrall KK, Vaughn EM, Roof MB, Meng XJ (2010). Development of SYBR green-based real-time PCR and duplex nested PCR assays for quantitation and differential detection of species- or type-specific porcine Torque teno viruses. Journal of Virological Methods. 170(1-2):140-146. (Abstract)
Huang YW, Harrall KK, Dryman BA, Beach NM, Kenney SP, Opriessnig T, Vaughn EM, Roof MB, Meng XJ (2011). Expression of the putative ORF1 capsid protein of Torque teno sus virus 2 (TTSuV2) and development of Western blot and ELISA serodiagnostic assays: correlation between TTSuV2 viral load and IgG antibody level in pigs. Virus Research. 158(1-2):79-88. (Abstract)
Huang YW, Ni YY, Dryman BA, Meng XJ (2010). Multiple infection of porcine Torque teno virus in a single pig and characterization of the full-length genomic sequences of four U.S. prototype PTTV strains: Implication for genotyping of PTTV. Virology. 396(2):289-297. (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)