Effect of Dengue Virus Infection on Fc-receptor Functions of Mouse Macrophages

Chaturvedi, U. C.; Nagar, Rachna; Mathur, Asha

doi:10.1099/0022-1317-64-11-2399

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…The involvement of FcγRIIB in virus neutralization is thus unique and shows that ligation of FcγRIIB impairs phagocytosis and antibody-dependent enhancement in monocytes. Our observations may also explain previously reported observations of peak antibody titers following acute influenza or dengue infections being associated with transient reduction in the phagocytic activity of macrophages in experimental mouse models (39,40).…”

Section: Discussionsupporting

confidence: 90%

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Chan

Zhang²,

Tan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

136

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The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. D engue is the most common mosquito-borne viral disease globally. The lack of an effective preventive measure, especially a licensed vaccine, has resulted in the global spread of this virus (1, 2). Although neutralizing antibodies can confer lifelong immunity against reinfection by one of the four dengue virus (DENV) serotypes, subneutralizing antibody levels or crossreactive antibodies appear to enhance the risk of severe dengue in subsequent infections (3-6). DENV bound with subneutralizing concentrations of antibody has been shown to result in increased virus uptake and replication in Fc gamma receptor (FcγR)-bearing cells such as monocytes/macrophages (4, 7). Thus, defining the determinants for virus neutralization will be important for the design of an effective dengue vaccine that protects against all four DENV serotypes while minimizing the risk of antibodydependent enhancement of DENV infection.Neutralization of flavivirus infection is a multiple-hit phenomenon. Recent stoichiometric studies have shown that both antibody affinity and epitope accessibility are important determinants for virus neutralization (8-10). Antibodies neutralize DENV by either preventing virus attachment to cellular receptors (11) or inhibiting viral fusion intracellularly (12). However, whether the antibody blocks attachment or fusion, the resulting immune complex is expected to be cleared from the circulation by professional phagocytes, especially the FcγR-bearing cells. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by ...

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Section: Discussionsupporting

confidence: 90%

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Chan

Zhang²,

Tan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

128

136

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“…The slide was then examined under an oil immersion lens (100×) for cells containing intracellular latex particles. On each slide 200 to 300 cells were counted and the data presented as a percentage of phagocytic cells (Chaturvedi et al 1983). …”

Section: Phagocytic Activity Of Splenic Macrophagesmentioning

confidence: 99%

Effects of Dengue Virus Infection on the Spleen of Male Mice Given Hexavalent Chromium with Drinking Water

Shrivastava

Upreti

Chaturvedi

2005

Toxicology Mechanisms and Methods

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The present study was undertaken to investigate the effects of dengue virus (DV) infection in male mice given drinking water containing 250 ppm Cr (VI) and the normal control male mice given plain water to drink. On the basis of intake of water in 24 h, the average dose of Cr (VI) in each mouse was 14.8 mg/kg. After 3, 6, and 9 weeks of drinking Cr (VI), a set of five mice from each group were inoculated intracerebrally (ic) with a 1000 x LD(50) (100 times the lethal dose that kills 50% mice) dose of DV, and the effects on the spleen were studied at the fourth and eightth day postinoculation. It was observed that Cr (VI) drinking and DV infection led to reduction in the weight of the spleen, but the peak reduction was seen in Cr (VI)-fed mice infected with DV, being 30, 34, and 61% at 3, 6, and 9 weeks respectively. A similar response was seen with respect to the cytotoxic activity of spleen homogenates, phagocytic activity of macrophages, and the mitogenic response of spleen cells to concanavalin A from different groups of animals, being most marked (58 to 60%) at the ninth week of Cr (VI) drinking. This shows a summation of adverse effects of DV infection in mice preexposed to Cr (VI).

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“…The virus antigen is detectable in the spleen of mice, inoculated intraccrebrally with DV by itnmunolluorescence from day 4 and the titre of the virus reaches peak levels from day 8 [17]. The CF is detectable in the spleens of such mice from day 6, reaching peak cytotoxic activity on days 10-11 [I].…”

Section: Discussionmentioning

confidence: 99%

Dengue virus-induced human cytotoxic factor: production by peripheral blood leucocytes in vitro

Mukerjee¹,

Chaturvedi²,

Dhawan³

1995

Clinical and Experimental Immunology

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SUMMARYDuring dengue type 2 virus (DV) infection of mice a unique cytokine. the cytotoxic factor (CF), is produced which reproduces the pathological lesions seen in patients of dengue haemorrhagic fever (DHF). Recently we have observed a CF-like protein in the sera of DHF cases. The present study was undertaken to investigate whether DV can stimulate human peripheral blood mommLiclear cells (PBMC) in viiro to produce human CF (hCF). Cultures prepared from PBMC or its enriched subpopulations were inoculated with 1000 LDj,, of DV and controls with normal mouse brain suspension (NMB). Aliquots of cultures were harvested daily from 24 h to 96 h and their supernatant (CS) and cells were separated. CS were screened for viral titrcs and for the presence of hCF by cytotoxicity assay, inhibition ELISA. dot blot and Western blot tests using anti-mouse-CF antibodies. The RNA from the cells was screened in Northern blot and dot blot tests for the presence of mRNA for CF. It was observed that hCF appeared in the CS of DV-infected culture of PBMC and T-enriched cells at 48 h and was present until 96 h; no CF was detected in CS of B cells or monocyte cultures. The production of hCF was abrogated by pretreatment oi' the T cells with anti-CD4 antibodies but not with anti-CDS antibodies, indicating that hCF was produced by CD4 T ceils. The Northern blot analysis using oligonucleotide probes prepared on the basis of amino-terminal sequence of mouse CF, showed presence of niRNA for hCF in PBMC and T cell cultures. DV replicated in PBMC cultures with peak titres at 48 h. The findings ofthe present study demonstrate that DV-induced hCF is produced by human T cells.

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Effect of Dengue Virus Infection on Fc-receptor Functions of Mouse Macrophages

Cited by 16 publications

References 22 publications

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

Effects of Dengue Virus Infection on the Spleen of Male Mice Given Hexavalent Chromium with Drinking Water

Dengue virus-induced human cytotoxic factor: production by peripheral blood leucocytes in vitro

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