D W Trent

University of Texas Medical Branch at Galveston, Galveston, Texas, United States

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Publications (118)417.03 Total impact

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    ABSTRACT: Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.
    No preview · Article · Nov 2013 · Biologicals
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    ABSTRACT: Serial passaging of yellow fever virus 17D in Vero cells was employed to derive seed material for a novel inactivated vaccine, XRX-001. Two independent passaging series identified a novel lysine to arginine mutation at amino acid 160 of the envelope protein, a surface-exposed residue in structural domain I. A third passage series resulted in an isoleucine to methionine mutation at residue 113 of the NS4B protein, a central membrane spanning region of the protein which has previously been associated with Vero cell adaptation of other mosquito-borne flaviviruses. These studies confirm that flavivirus adaptation to growth in Vero cells can be mediated by structural or non-structural protein mutations.
    No preview · Article · Apr 2013 · Virus Research
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    Justin G Julander · Dennis W Trent · Thomas P Monath
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    ABSTRACT: Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes rare, serious adverse events resulting from active replication in the host and direct viral injury to vital organs. We recently reported development of a potentially safer β-propiolactone-inactivated whole virion YF vaccine (XRX-001), which was highly immunogenic in mice, hamsters, monkeys, and humans [10,11]. To characterize the protective efficacy of neutralizing antibodies stimulated by the inactivated vaccine, graded doses of serum from hamsters immunized with inactivated XRX-001 or live 17D vaccine were transferred to hamsters by the intraperitoneal (IP) route 24h prior to virulent, viscerotropic YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in the sera of treated animals 4h before challenge and 4 and 21 days after challenge. Neutralizing antibodies were shown to mediate protection. Animals having 50% plaque reduction neutralization test (PRNT(50)) titers of ≥40 4h before challenge were completely protected from disease as evidenced by viremia, liver enzyme elevation, and protection against illness (weight change) and death. Passive titers of 10-20 were partially protective. Immunization with the XRX-001 vaccine stimulated YF neutralizing antibodies that were equally effective (based on dose response) as antibodies stimulated by live 17D vaccine. The results will be useful in defining the level of seroprotection in clinical studies of new yellow fever vaccines.
    Full-text · Article · Jun 2011 · Vaccine
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    ABSTRACT: Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).
    Full-text · Article · Apr 2011 · New England Journal of Medicine
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    ABSTRACT: In May 2009, a group of international experts on dengue, vaccine quality and clinical evaluation met together (i) to review disease, vaccine pipeline, quality issues in manufacturing, issues of environmental risk assessment, nonclinical and clinical evaluation of live recombinant dengue vaccines and (ii) to initiate revising WHO guidelines for the production and quality control of candidate tetravalent dengue vaccines (live). This report summarizes an exchange of views on scientific and technical issues related to the quality, safety and efficacy of candidate dengue vaccines. Recognizing live dengue vaccines are the major vaccines in the clinical pipeline, the Working Group agreed (i) to focus on live dengue vaccines in the revision of the WHO guidelines and (ii) to add new guidelines on nonclinical and clinical evaluation, and environmental risk assessment for live dengue vaccines in the revision.
    No preview · Article · Oct 2010 · Vaccine
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    ABSTRACT: In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P<0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.
    No preview · Article · Mar 2010 · Vaccine
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    ABSTRACT: Introduction of the polymerase chain reaction (PCR) technique as a rapid and sensitive method for amplification of DNA has resulted in development of new specific nucleic acid-based techniques for clinical diagnosis of infections (1). Improvements in nucleic acid amplification by PCR, and development of sensitive nonisotopic technologies for detection of amplified viral genes have facilitated the introduction of molecular methods into the diagnostic laboratory. The availability of simple and well-characterized protocols, cominercial reagents of high quality, improved equipment for performing PCR reactions, and nonisotopic methods for detection of amplicons has stimulated development of PCR-based tests for detection of both DNA and RNA viral nucleic acids in clinical samples (1).
    No preview · Chapter · Jan 2008
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    ABSTRACT: St. Louis encephalitis (SLE) and West Nile (WN) flaviviruses are genetically closely related and cocirculate in the United States. Virus neutralization tests provide the most specific means for serodiagnosis of infections with these viruses. However, use of wild-type SLE and WN viral strains for laboratory testing is constrained by the biocontainment requirements. We constructed two highly attenuated yellow fever (YF) virus chimeras that contain the premembrane-envelope (prM-E) protein genes from the virulent MSI-7 (isolated in the United States) or the naturally attenuated CorAn9124 (Argentina) SLE strains. The YF/SLE (CorAn version) virus and the previously constructed YF/WN chimera were shown to specifically distinguish between confirmed human SLE and WN cases in a virus neutralization test using patient sera. These chimeras have the potential for use as diagnostic reagents and vaccines against SLE and WN.
    Preview · Article · Dec 2004 · The American journal of tropical medicine and hygiene
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    ABSTRACT: The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN02 vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.
    Preview · Article · Dec 2004 · Journal of Virology
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    ABSTRACT: The ability of antisera raised against a candidate Japanese encephalitis virus (JEV) vaccine, ChimeriVax-JE, and the currently licensed vaccine, JE-VAX, to protect against strains of JEV representing the four major genotypes was assessed. Neutralization assays and passive protection studies in mice showed that greatest protection was provided against strains of genotypes II and III, although some protection was also afforded against genotypes I and IV strains. ChimeriVax-JE stimulated protection that was comparable or superior to the JE-VAX control.
    No preview · Article · Oct 2004 · Vaccine
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    ABSTRACT: To construct chimeric YF/DEN viruses (ChimeriVax-DEN), the premembrane (prM) and envelope (E) genes of yellow fever (YF) 17D virus were replaced with those of each wild-type (WT) dengue (DEN) virus representing serotypes 1 to 4. ChimeriVax-DEN1-4 vaccine viruses were prepared by electroporation of Vero cells with RNA transcripts prepared from viral cDNA (F. Guirakhoo, J. Arroyo, K. V. Pugachev, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Soike, M. Ratteree, and T. P. Monath, J. Virol. 75:7290-7304, 2001; F. Guirakhoo, K. Pugachev, J. Arroyo, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Draper, and T. P. Monath, Virology 298:146-159, 2002). Progeny viruses were subjected to three rounds of plaque purifications to produce the Pre-Master Seed viruses at passage 7 (P7). Three further passages were carried out using U.S. current Good Manufacturing Practices (cGMP) to produce the Vaccine Lot (P10) viruses. Preclinical studies demonstrated that the vaccine candidates are replication competent and genetically stable and do not become more neurovirulent upon 20 passages in Vero cells. The safety of a tetravalent vaccine was determined and compared to that of YF-VAX in a formal monkey neurovirulence test. Brain lesions produced by the tetravalent ChimeriVax-DEN vaccine were significantly less severe than those observed with YF-VAX. The immunogenicity and protective efficacy of four different tetravalent formulations were evaluated in cynomolgus monkeys following a single-dose subcutaneous vaccination followed by a virulent virus challenge 6 months later. All monkeys developed low levels of viremia postimmunization, and all the monkeys that had received equal concentrations of either a high-dose (5,5,5,5) or a low-dose (3,3,3,3) formulation seroconverted against all four DEN virus serotypes. Twenty-two (92%) of 24 monkeys were protected as determined by lack of viremia post-challenge. This report is the first to demonstrate the safety of a recombinant DEN virus tetravalent vaccine in a formal neurovirulence test, as well as its protective efficacy in a monkey challenge model.
    Full-text · Article · Jun 2004 · Journal of Virology
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    ABSTRACT: Three consecutive plaque purifications of four chimeric yellow fever virus-dengue virus (ChimeriVax-DEN) vaccine candidates against dengue virus types 1 to 4 were performed. The genome of each candidate was sequenced by the consensus approach after plaque purification and additional passages in cell culture. Our data suggest that the nucleotide sequence error rate for SP6 RNA polymerase used in the in vitro transcription step to initiate virus replication was as high as 1.34 × 10−4 per copied nucleotide and that the error rate of the yellow fever virus RNA polymerase employed by the chimeras for genome replication in infected cells was as low as 1.9 × 10−7 to 2.3 × 10−7. Clustering of beneficial mutations that accumulated after multiple virus passages suggests that the N-terminal part of the prM protein, a specific site in the middle of the E protein, and the NS4B protein may be essential for nucleocapsid-envelope interaction during flavivirus assembly.
    Preview · Article · Feb 2004 · Journal of Virology
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    ABSTRACT: Yellow fever, dengue, Japanese encephalitis and tick-borne encephalitis viruses are the medically most important members of the Flavivirus genus composed primarily of arboviruses. In this paper, we review the commercially available traditional flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis, as well as modern approaches to flavivirus vaccines. Formalin inactivation technology has been employed to produce killed vaccines. Flaviviruses have been attenuated by multiple passages in animal tissues and cell cultures to produce empirical live attenuated vaccines. The use of traditional methods is being pursued to develop vaccines against other flavivirus diseases, such as dengue, and to improve existing vaccines, such as for Japanese encephalitis. With the recent development of infectious clones, rational approaches to attenuated flavivirus vaccines have employed the introduction of specific mutations into wild type viruses and chimerisation between different viruses. Novel methods for delivery of live vaccines, such as inoculation of infectious DNA or RNA, have been described. Other approaches, such as the construction of protein subunit, expression vector-based and naked DNA vaccines, have been proposed to create alternate vaccine candidates.
    No preview · Article · Jun 2003 · International Journal for Parasitology
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    R.S. Lanciotti · D.J. Gubler · D.W. Trent
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    ABSTRACT: Nucleotide sequences of the envelope protein genes of 19 geographically and temporally distinct dengue (DEN)-4 viruses were determined. Nucleic acid sequence comparison revealed that the identity among the DEN-4 viruses was greater than 92%. Similarity among deduced amino acids was between 96 and 100%; in most cases identical amino acid substitutions occurred among viruses from similar geographical regions. Alignment of nucleic acid sequences followed by parsimony analysis generated phylogenetic trees, which indicated that geographically independent evolution of DEN-4 viruses had occurred. DEN-4 viruses were separated into two genetically distinct subtypes (genotypes). Genotype-1 contains viruses from the Philippines, Thailand and Sri Lanka; genotype-2 consists of viruses from Indonesia, Tahiti, the Caribbean Islands (Puerto Rico, Dominica) and Central and South America.
    Full-text · Article · Oct 1997 · Journal of General Virology
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    V F Yamshchikov · D W Trent · R W Compans
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    ABSTRACT: Recently, we have shown that the ability of the flavivirus NS2B-NS3 protease complex to promote efficient signalase processing of the C-prM precursor, as well as secretion of prM and E, does not appear to depend strictly on cleavage of the precursor at its Lys-Arg-Gly dibasic site by the protease. We suggested that the association of the protease with the precursor via NS2B may be sufficient by itself for the above effects. To study the proposed association in more detail, we have developed an assay in which processing at the C-prM dibasic cleavage site is abolished by Lys-->Gly conversion. We constructed deletion mutants and chimeras of the West Nile (WN) flavivirus NS2B protein and expressed them in the context of [5'-C-->NS3(243)] containing either wild-type C-prM or its cleavage site mutant. All NS2B variants were able to form active protease complexes. Deletion of the carboxy-terminal cluster of hydrophobic amino acids in NS2B had no apparent effect on the formation of prM and prM-E secretion for the cassettes containing either wild-type or mutated C-prM precursor. Deletion of the amino-terminal hydrophobic cluster in NS2B did not affect prM-E secretion for the cassettes with wild-type C-prM but abrogated prM-E secretion for the cassettes with the mutated dibasic cleavage site in C-prM. Similarly, the NS2B-NS3(178) protease of Japanese encephalitis (JE) virus, when substituted for the WN virus NS2B-NS3(243) protease, was able to promote prM-E secretion for the cassette with the wild-type C-prM precursor but not with the mutated one. Replacement of the deleted amino-terminal hydrophobic cluster in the WN virus NS2B protein with an analogous JE virus sequence restored the ability of the protease to promote prM-E secretion. On the basis of these observations, roles of individual protease components in upregulation of C-prM signalase processing are discussed.
    Preview · Article · Jul 1997 · Journal of Virology
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    ABSTRACT: The evolution of yellow fever virus over 67 years was investigated by comparing the nucleotide sequences of the envelope (E) protein genes of 20 viruses isolated in Africa, the Caribbean, and South America. Uniformly weighted parsimony algorithm analysis defined two major evolutionary yellow fever virus lineages designated E genotypes I and II. E genotype I contained viruses isolated from East and Central Africa. E genotype II viruses were divided into two sublineages: IIA viruses from West Africa and IIB viruses from America, except for a 1979 virus isolated from Trinidad (TRINID79A). Unique signature patterns were identified at 111 nucleotide and 12 amino acid positions within the yellow fever virus E gene by signature pattern analysis. Yellow fever viruses from East and Central Africa contained unique signatures at 60 nucleotide and five amino acid positions, those from West Africa contained unique signatures at 25 nucleotide and two amino acid positions, and viruses from America contained such signatures at 30 nucleotide and five amino acid positions in the E gene. The dissemination of yellow fever viruses from Africa to the Americas is supported by the close genetic relatedness of genotype IIA and IIB viruses and genetic evidence of a possible second introduction of yellow fever virus from West Africa, as illustrated by the TRINID79A virus isolate. The E protein genes of American IIB yellow fever viruses had higher frequencies of amino acid substitutions than did genes of yellow fever viruses of genotypes I and IIA on the basis of comparisons with a consensus amino acid sequence for the yellow fever E gene. The great variation in the E proteins of American yellow fever virus probably results from positive selection imposed by virus interaction with different species of mosquitoes or nonhuman primates in the Americas.
    Full-text · Article · Oct 1995 · Journal of Virology
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    L.R. Jan · C.S. Yang · D.W. Trent · B Falgout · C.J. Lai
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    ABSTRACT: Processing of Japanese encephalitis (JE) virus non-structural (NS) proteins expressed by recombinant vaccinia viruses was analysed to characterize the responsible viral protease. Analysis of the processing of polyprotein NS2A-2B-3' containing the N-terminal 322 amino acids of NS3 revealed products consistent with cleavages at the predicted intergenic junctions as well as at one or possibly two sites within NS2A. Cleavage at the alternate site(s) containing the cleavage sequence motif within NS2A could possibly explain the production of the NS1' protein in JE virus-infected cells. Polyprotein NS2A-d2B-3' containing a large deletion within NS2B was cleavage-defective, despite the presence of the proposed NS3 protease domain. Cleavage of NS2A-d2B-3' was restored if NS2B or NS2A-2B was supplied in trans, providing evidence that NS2B is strictly required for NS3 proteolytic activity. NS2B- or NS3-specific sera raised against the bacterial TrpE fusion protein co-precipitated NS2B and NS3 or NS3' from the lysate of JE virus or recombinant virus-infected cells. Thus both protease components are associated as a complex, presumably representing the active JE virus protease. JE virus and the analogous dengue 4 (DEN-4) protease components were employed to examine the activity of heterologous proteases. The defective cleavage of JE virus NS2A-d2B-3' was complemented by heterologous DEN-4 NS2B, whereas the defective cleavage of DEN-4 NS2A-d2B-3' was not corrected by heterologous JE virus NS2B. This suggests that the heterologous JE virus NS2B-DEN-4 NS3 protease is not active, despite the considerable sequence conservation of NS2B and NS3 between the two viruses. The cleavage activity was restored by replacement of the C-terminal 80 amino acids of JE virus NS2B with the corresponding DEN-4 sequence, consistent with the notion that the C-terminal region contains amino acid residues for interaction with DEN-4 NS3.
    Preview · Article · Apr 1995 · Journal of General Virology
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    HL NI · G.-J. J. Chang · H Xie · D W Trent · A. D. T. Barrett
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    ABSTRACT: To identify the molecular determinants for attenuation of wild-type Japanese encephalitis (JE) virus strain SA14, the RNA genome of wild-type strain SA14 and its attenuated vaccine virus SA14-2-8 were reverse transcribed, amplified by PCR and sequenced. Comparison of the nucleotide sequence of SA14-2-8 vaccine virus with virulent parent SA14 virus and with two other attenuated vaccine viruses derived from SA14 virus (SA14-14-2/PHK and SA14-14-2/PDK) revealed only seven amino acids in the virulent parent SA14 had been substituted in all three attenuated vaccines. Four were in the envelope (E) protein (E-138, E-176, E-315 and E-439), one in non-structural protein 2B (NS2B-63), one in NS3 (NS3-105), and one in NS4B (NS4B-106). The substitutions at E-315 and E-439 arose due to correction of the SA14/CDC sequence published previously by Nitayaphan et al. (Virology 177, 541-552, 1990). The mutations in NS2B and NS3 are in functional domains of the trypsin-like serine protease. Attenuation of SA14 virus may therefore, in part, be due to alterations in viral protease activity, which could affect replication of the virus.
    Full-text · Article · Mar 1995 · Journal of General Virology
  • Daniel G. Sullivan · G J Chang · Dennis W. Trent · Ramesh K. Akkina
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    ABSTRACT: Border disease virus (BDV) of sheep, an important ovine pathogen, is serologically related to the two other well characterized members of the Pestivirus genus of the Flaviviridae family, namely bovine viral diarrhea virus (BVDV) and hog cholera virus (HoCV). To determine its genetic relationship to BVDV and HoCV, the genome of BDV strain, BD-78 encompassing the 5' untranslated region (UTR) and structural gene coding region was molecularly cloned and the nucleotide sequence determined. The sequenced region of 3,567 nucleotides contained one open reading frame encoding 1063 amino acids. The nucleotide and amino acid sequences of BD-78 were compared with those of two BVDV strains NADL and SD-1, and the Alfort and Brescia strains of HoCV. The overall nucleotide sequence homologies of the region sequenced of BD-78 are 68.3% with BVDV-NADL, 67.8% with BVDV-SD-1, 69.0% with HoCV-Brescia, and 65.8% with HoCV-Alfort. The overall amino acid sequence homologies of BD-78 are 76.1% with NADL, 76.5% with SD-1, 74.2% with Brescia, and 72.9% with Alfort. The most conserved nucleotide and amino acid sequences between BD-78 and the other pestivirueses are in the 5' UTR and the capsid protein coding region (p14), where as the most divergent sequences are in the E2 coding region. These findings suggest that BDV is a unique virus in the Pestivirus genus.
    No preview · Article · Oct 1994 · Virus Research
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    ABSTRACT: Nucleotide sequences of the 5' non-coding region and the structural protein genes of the live, attenuated Japanese encephalitis vaccine virus strains SA14-2-8 and SA14-5-3 and the wild-type parental strain SA14/USA were determined. SA14-2-8 differed from SA14/USA by 13 nucleotides and eight amino acids whereas SA14-5-3 differed from SA14/USA by 15 nucleotides and eight amino acids. A comparison of the 5' non-coding region and amino acid sequences of the structural proteins of these two attenuated vaccine strains and of vaccine strains SA14-14-2/PHK and SA14-14-2/PDK with three sequences of their wild-type parent SA14 virus was performed. This revealed only two common amino acid substitutions at positions 138 and 176 in the envelope (E) protein. The substitution at E138 was predicted to cause a change in the secondary structure of the E protein. These two amino acid substitutions in the E protein may contribute to attenuation of the Japanese encephalitis vaccine viruses.
    Full-text · Article · Jul 1994 · Journal of General Virology

Publication Stats

6k Citations
417.03 Total Impact Points


  • 2013
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States
  • 1992-1995
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
  • 1993
    • University of California, San Diego
      San Diego, California, United States
  • 1985-1993
    • Centers for Disease Control and Prevention
      • Division of Vector-Borne Diseases
      Druid Hills, GA, United States
    • Monash University (Australia)
      • Department of Microbiology
      Melbourne, Victoria, Australia
  • 1979-1991
    • Colorado State University
      Fort Collins, Colorado, United States
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • Colorado Department of Public Health and Environment
      Denver, Colorado, United States
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1982-1990
    • U.S. Department of Health and Human Services
      Washington, Washington, D.C., United States
  • 1989
    • University of Houston
      Houston, Texas, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1985-1987
    • California Institute of Technology
      • Division of Biology
      Pasadena, California, United States
  • 1986
    • Rochester General Hospital
      Rochester, New York, United States
  • 1976-1984
    • University of Texas Health Science Center at San Antonio
      • Department of Microbiology and Immunology
      San Antonio, Texas, United States
  • 1983
    • Honolulu University
      Honolulu, Hawaii, United States
  • 1981
    • North Carolina State University
      • Department of Microbiology
      Raleigh, North Carolina, United States
  • 1971
    • Brigham Young University - Provo Main Campus
      Provo, Utah, United States