Biologic Properties of Dengue Viruses Following Serial Passage in Primary Dog Kidney Cells: Studies at the University of Hawaii

Halstead, Scott B.; Marchette, Nyven J.

doi:10.4269/ajtmh.2003.69.6_suppl.0690005

Cited by 67 publications

(45 citation statements)

References 17 publications

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“…In contrast the 16007/ V virus, which also plaques well in Vero cells had a better infectivity profile for rhesus monkeys causing viremia almost 10-fold higher with much longer duration. Viremia and seroconversion in all recipient animals after inoculation of rhesus monkeys with DENV-1 16007 has been reported (Halstead et al 1973a, Halstead & Marchette 2003. Halstead et al (1973a) observed that most rhesus monkeys receiving the 16007 virus had viremias for 5-6 days a result which is similar to ours.…”

Section: Discussionsupporting

confidence: 82%

“…It belongs to genotype II (Southeast Asia/South Pacific; Rico-Hesse 2003). The virus was propagated by serial passages in BSC-1 (3 times) cells, in LLC-MK 2 (4 times) and two more in T. amboinensis mosquitoes (Halstead & Marchette 2003). It was further passaged in C6/36 cells another 5 times.…”

Section: Denv-3 H87mentioning

confidence: 99%

“…DENV-1 16007/V and 16007/C -The 16007 virus belongs to genotype II (Gonçalvez et al 2002) or the Thailand genogroup and was isolated from serum of a DHF case in the Thailand by passaging 3 times in BSC-1 cells, 7 times in LLC-MK 2 and two more in Toxorynchites amboinensis mosquitoes (Halstead & Marchette 2003). In Bio-Manguinhos it was passaged 3 times in C6/36, one in Vero cells for the preparation of the working seed (16007/V; 6.9 log 10 PFU/ml) and an additional passage in C6/36 for preparation of the 16007/C stock (5.8 log 10 PFU/ml).…”

Section: Virusesmentioning

confidence: 99%

“…The next step for testing a candidate vaccine is the study of its immunogenicity in a nonhuman primate model. Although some hallmarks of dengue severe syndromes have been described (Halstead et al 1973a,b), it is widely accepted that the main parameters to be considered are neutralizing antibodies induced by the vaccine candidate and the magnitude and duration of peripheral viremia upon challenge of previously immunized animals (Halstead & Marchette 2003, Raviprakash et al 2003, Hanley et al 2004, Guirakhoo et al 2004, Blaney et al 2005, Sun et al 2006). In our efforts to develop a live attenuated dengue vaccine based on chimeric VF 17D viruses (Caufour et al 2001, Mateu et al 2007 we needed to establish a nonhuman primate model to test the protective capability of the recombinant viruses.…”

mentioning

confidence: 99%

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<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

Freire¹,

Marchevsky²,

Almeida³

et al. 2007

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 82%

Section: Denv-3 H87mentioning

confidence: 99%

Section: Virusesmentioning

confidence: 99%

mentioning

confidence: 99%

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<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

Freire¹,

Marchevsky²,

Almeida³

et al. 2007

Mem. Inst. Oswaldo Cruz

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“…Our results showed that the MID 50 4 FFU for its derived attenuated vaccine (18,35). Conceivably, the infectivity of DENVs depends on the serotype and passage history.…”

Section: Discussionmentioning

confidence: 88%

Epitope Determinants of a Chimpanzee Dengue Virus Type 4 (DENV-4)-Neutralizing Antibody and Protection against DENV-4 Challenge in Mice and Rhesus Monkeys by Passively Transferred Humanized Antibody

Lai

Goncalvez

Men

et al. 2007

J Virol

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The chimpanzee monoclonal antibody (MAb) 5H2 is specific for dengue virus type 4 (DENV-4) and neutralizes the virus at a high titer in vitro. The epitope detected by the antibody was mapped by sequencing neutralization escape variants of the virus. One variant contained a Lys 174 -Glu substitution and another contained a Pro 176 -Leu substitution in domain I of the DENV-4 envelope protein (E). These mutations reduced binding affinity for the antibody 18-to >100-fold. Humanized immunoglobulin G (IgG) 5H2, originally produced from an expression vector, has been shown to be a variant containing a nine-amino-acid deletion in the Fc region which completely ablates antibody-dependent enhancement of DENV replication in vitro. The variant MAb, termed IgG 5H2 ⌬D, is particularly attractive for exploring its protective capacity in vivo. Passive transfer of IgG 5H2 ⌬D at 20 g/mouse afforded 50% protection of suckling mice against challenge with 25 50% lethal doses of mouse neurovirulent DENV-4 strain H241. Passive transfer of antibody to monkeys was conducted to demonstrate proof of concept for protection against DENV challenge. Monkeys that received 2 mg/kg of body weight of IgG 5H2 ⌬D were completely protected against 100 50% monkey infectious doses (MID 50 ) of DENV-4, as indicated by the absence of viremia and seroconversion. A DENV-4 escape mutant that contained a Lys 174 -Glu substitution identical to that found in vitro was isolated from monkeys challenged with 10 6 MID 50 of DENV-4. This substitution was also present in all naturally occurring isolates belonging to DENV-4 genotype III. These studies have important implications for possible antibody-mediated prevention of DENV infection.The four dengue virus serotypes (dengue virus types 1 to 4 [DENV-1 to DENV-4]) cause more morbidity in humans than any other arthropod-borne flaviviruses (40). Up to 100 million DENV infections occur every year, mostly in tropical and subtropical areas where the vector mosquitoes, principally Aedes aegypti and Aedes albopictus, are present. Dengue illnesses range from mild fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which has fatality rates ranging from Ͻ1% to 5% in children. The most severe dengue (Ͼ90% fatality rate) occurs in patients reinfected with DENV of a serotype different from that in the primary infection (15, 50). Antibody-dependent enhancement (ADE) of DENV replication has been proposed as an underlying pathogenic mechanism of severe DHF/DSS (17). A safe and effective vaccine against dengue is still not available.Early studies of DENV infections in human volunteers showed that homotypic immunity against the same serotype is life-long but that heterotypic immunity against other serotypes lasts only months (49). Since antibodies provide the important component of acquired immunity against infection, type-specific immunity afforded by antibody may contribute significantly to long-term protection. Antigenic differences exist among strains of the same serotype (21). DENV variants that form ...

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Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells

Kou

Quinn

Chen

et al. 2007

Journal of Medical Virology

178

160

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A better understanding of the pathogenesis of dengue hemorrhagic fever and dengue shock syndrome requires the precise identification of dengue virus (DV) permissive target cells. To examine the relative DV permissiveness among cell subsets, we inoculated unfractionated human peripheral blood mononuclear cells with DV2-16681 in the presence or absence of pooled DV-immune human sera (PHS), and assessed infection with fluorescent dye labeled DV-specific monoclonal antibody and cell surface markers using flow cytometry. We found significantly higher levels of DV antigen staining on DVinfected than mock-infected primary monocytes (3.54 AE 3.42% vs. 0.50 AE 0.38%; P ¼ 0.001). The magnitude of infection was markedly enhanced in the presence of highly diluted PHS (10.04 AE 6.10% vs. 3.54 AE 3.42%; P ¼ 0.015). Under identical experimental conditions, primary T or B cells were not infected either with or without the addition of PHS (0.06 AE 0.04% and 0.44 AE 0.22% for T and B cells, respectively). Furthermore, depletion of CD14þ monocytes prior to DV inoculation abrogated the detection of infected cells, and the addition of monoclonal antibodies to either FcgRI (CD64) or FcgRII (CD32) led to a 50-70% reduction in antibody-dependent enhancement (ADE) of DV infection. Collectively, these results provide further support to the notion that primary monocytes and FcgRs expressed on these cells may be important in the initial steps of immune enhancement observed in some patients with natural DV infection. They also demonstrate that using modern experimental technology, DV infection, and neutralization and enhancement of DV infection can be easily assessed simultaneously in multiple cell types.

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Biologic Properties of Dengue Viruses Following Serial Passage in Primary Dog Kidney Cells: Studies at the University of Hawaii

Cited by 67 publications

References 17 publications

<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

<![CDATA[<B>Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys</B>]]>

Epitope Determinants of a Chimpanzee Dengue Virus Type 4 (DENV-4)-Neutralizing Antibody and Protection against DENV-4 Challenge in Mice and Rhesus Monkeys by Passively Transferred Humanized Antibody

Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells

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