Evidence for antigen production in muscles by dengue and Japanese encephalitis DNA vaccines and a relation to their immunogenicity in mice

Konishi, Eiji; Terazawa, Aya; Fujii, Atsuko

doi:10.1016/s0264-410x(03)00376-1

Cited by 33 publications

(20 citation statements)

References 42 publications

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“…In contrast to our results, Chang et al (2003) could not detect secretion of the prM or E proteins from COS cells transiently expressing the DENV-2 prM and E genes and suggested that an ER-retention signal resides in the stem-anchor region of the E protein. However, a number of other studies have reported the secretion of DENV RSPs from mammalian cells expressing the DENV prM and E genes, either transiently (Fonseca et al, 1994;Raviprakash et al, 2000) or stably (Konishi & Fujii, 2002;Konishi et al, 2003). Previous studies have determined that furin-mediated cleavage of prM was necessary to activate the full fusogenic potential of flaviviruses (Guirakhoo et al, 1991(Guirakhoo et al, , 1992Stadler et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly

Pryor

Azzola

Wright

et al. 2004

Journal of General Virology

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The mature flavivirus particle comprises a nucleocapsid core surrounded by a lipid bilayer containing the membrane (M) (derived from the precursor prM) and envelope (E) proteins. The formation of intracellular prM/E heterodimers occurs rapidly after translation and is believed to be important for the assembly and secretion of immature virus particles. In this study, the role of the His residue at position 39 in the M protein (M39) of dengue virus type 2 (DENV-2) in the virus life cycle was investigated. Mutations encoding basic (Arg), non-polar (Leu and Pro) and uncharged polar (Asn, Gln and Tyr) amino acids at M39 were introduced into a DENV-2 genomic-length cDNA clone and their effects on virus replication were examined. Substitution of the His residue with non-polar amino acids abolished virus replication, whereas substitution with basic or uncharged polar amino acids decreased virus replication moderately (~2 log 10 p.f.u. ml "1 decrease in viral titre for Arg and Asn) or severely (>3?5 log 10 p.f.u. ml "1 decrease in viral titre for Gln and Tyr). Selected mutations were introduced into a prM-E gene cassette and expressed transiently in COS cells to investigate whether the mutations impaired prM/E association or secretion. None of the mutations was found to disrupt the formation of intracellular prM/E heterodimers. However, the mutations that abolished virus replication prevented secretion of prM/E complexes. The results of this study pinpoint a critical residue in the M protein that potentially plays a role in viral morphogenesis, secretion and entry. INTRODUCTIONDengue virus (DENV) is transmitted by mosquitoes and causes the most important arthropod-borne viral disease of humans, with 50-100 million individuals infected annually worldwide (Gubler, 2002). The four serotypes of DENV (1-4) are members of the genus Flavivirus within the family Flaviviridae, along with a number of other medically important viruses that include Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), West Nile virus (WNV) and yellow fever virus (YFV) (Burke & Monath, 2001).The mature flavivirus particle contains three structural proteins, the capsid (C), envelope (E) and membrane (M) (derived from the precursor prM) proteins, plus a lipid bilayer and a single strand of infectious RNA. The structure of the mature DENV-2 particle has been determined by fitting the X-ray crystallographic structure of the TBEV E protein (Rey et al., 1995) into a 24 Å resolution cryoelectron microscopic (cryo-EM) reconstruction of the DENV-2 particle (Kuhn et al., 2002). The structure revealed that 90 E protein dimers lying parallel to the membrane in a 'herringbone' conformation and 180 M proteins form a tightly packed outer icosahedral protein shell surrounding a lipid bilayer, which encloses a disordered nucleocapsid consisting of multiple copies of the C protein surrounding the RNA genome (Kuhn et al., 2002).The flavivirus RNA genome is approximately 11 kb in size and encodes a large polyprotein with the gene order NH 2 -C-prM-E-N...

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Section: Discussionmentioning

confidence: 99%

Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly

Pryor

Azzola

Wright

et al. 2004

Journal of General Virology

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“…DNA vaccine has shown no when combined with other candidates [57] (Table 2). In one of the combined immunization approaches DNA vaccines against tick-borne encephalitis viruses showed negligible interference thus DNA vaccines can be used in combination for achieving maximum results [54].…”

Section: Discussionmentioning

confidence: 99%

“…PcDNA3 based DNA vaccines using PrM and E gene prM and E expressed together produced extracellular sub-viral particles (EPS) in mammalian cells and were highly immunogenic [56,57]. In one of such vaccine strategy a pcDNA3-based DNA vaccine containing PrM/E genes of JEV, DENV1 and DENV2 was successful in producing strong neutralizing antibodies response in mice models [44,58].…”

Section: Different Approaches Used In Dna Vaccines Production Againstmentioning

confidence: 99%

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

Atif

Raheel

Imran

et al. 2016

JHVRV

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Dengue virus infections are a major cause of mortality and morbidity in Southeast Asia, South and Central America with 24'000 deaths annually. Two factors are accountable for the severe outcomes of Dengue Hemorrhagic Fever (DHF); one is the virulence of the virus and second is the cross-reactivity of various dengue serotypes with the immune system of the host. Rapid rise in the levels of various cytokines, particularly Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interleukin-8 (IL-8) have a major role in inducing distinctive clinical presentations of DHF. These range from simple plasma leakage to hemorrhagic problems and even shock. Another hallmark of DHF is the presence of cross reactive primary antibodies which produce an intense immune response in secondary infection resulting in immune mediated pathology seen in DHF. There have been many attempts made in the past for the development of a suitable vaccine for dengue fever. Vaccination using plasmid DNA against dengue fever is an active area of research. In this review the role of different cells in the multiplication of dengue virus and viral interactions with the immune system have been discussed. Special emphasis is given to the nature of DNA vaccines in general developmental efforts of a dengue fever vaccine.

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“…The serum samples used for evaluating EPs as ELISA antigens were those previously obtained from mice immunized with pcD2ME or pcJEME (28).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Extracellular Subviral Particles of Dengue Virus Type 2 and Japanese Encephalitis Virus Produced bySpodoptera frugiperdaCells for Use as Vaccine and Diagnostic Antigens

Kuwahara

Konishi

2010

Clin Vaccine Immunol

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Evidence for antigen production in muscles by dengue and Japanese encephalitis DNA vaccines and a relation to their immunogenicity in mice

Cited by 33 publications

References 42 publications

Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly

Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

Evaluation of Extracellular Subviral Particles of Dengue Virus Type 2 and Japanese Encephalitis Virus Produced bySpodoptera frugiperdaCells for Use as Vaccine and Diagnostic Antigens

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