Antibody‐Dependent Enhancement of Coxsackievirus B4 Infectivity of Human Peripheral Blood Mononuclear Cells Results in Increased Interferon‐α Synthesis
Centre Hospitalier Régional Universitaire de Lille, Lille, Nord-Pas-de-Calais, France The Journal of Infectious Diseases
(Impact Factor: 6).
11/2001; 184(9):1098-1108. DOI: 10.1086/323801
IgG devoid of neutralizing activity and isolated from donor plasma by chromatography formed immune complexes with coxsackievirus B4 (CVB4) and significantly increased the infection of peripheral blood mononuclear cells with CVB4. The major host cells for CVB4 infection enhanced with IgG are monocytic CD14+ cells. The roles of CVB and adenovirus receptor and Fcgamma receptor II and III have been shown. Increased viral replication and the release of infectious particles were demonstrated when interferon (IFN)-alpha produced by infected cells was first neutralized by use of antibodies. The CVB4 IgG-induced synthesis of IFN-alpha by monocytes reflected entry and uncoating of CVB4 but not of viral replication and required the presence of CVB4 RNA inside the cells. Thus, CVB4 can infect monocytes by an antibody-dependent mechanism through interactions between the virus, antiviral antibodies, and specific receptors that result in IFN-alpha production.
Available from: Huimin Yan
- "The results showed that preexisting antibodies against EV71 in local mucosal surfaces correlated with following viral infection , which suggesting an antibody dependent enhancement (ADE) of viral infection. The phenomenon of ADE has been documented for many viruses, including dengue virus, respiratory syncytial virus, human immunodeficiency virus, and Ebola virus (Girn et al., 2002; Halstead and O'Rourke, 1977; Hober et al., 2001). ADE was also observed in many members of the Picornaviridae family including poliovirus and enterovirus such as EV71, coxsackievirus B, which were identified for targeting macrophage and monocyte in vitro (Tirado and Yoon, 2003; Wang et al., 2010). "
[Show abstract] [Hide abstract]
ABSTRACT: Enterovirus 71 (EV71) infection causes severe central nervous system damage, particularly for children under the age of 5 years old, which remains a major public health burden worldwide. Clinical data released that children may be repeatedly infected by different members in enterovirus and get even worsen. Mucosa, especially epithelium of alimentary canal, was considered the primary site of EV71 infection. It has been elusive whether the preexsiting viral antibody in mucosa plays a role in EV71 infection. To answer this question, we respectively measured viral antibody response and EV71 RNA copy number of one hundred throat swab specimens from clinically confirmed EV71-infected children. The results released that low-level of mucosal IgG antibody against EV71 broadly existed in young population. More importantly, it further elucidated that the children with mucosal preexsiting EV71 IgG were prone to be infected, which suggested a former viral IgG mediated enhancement of viral infection in vivo.
Virologica Sinica 03/2015; 30(2). DOI:10.1007/s12250-014-3555-2
Available from: Gosse J Adema
- "Various studies have reported that HEV-B RNA can be detected in blood/PBMCs of type 1 diabetes patients , , although the source for the viral RNA remains unknown. Previous studies have shown that monocytes can be infected by HEV-B via antibody-dependent mechanisms , and more recently it has been described that pDCs become activated by CVB in an antibody-dependent fashion – although whether the virus also productively infects pDC was not extensively studied . Our data reveal that myeloid DCs can be infected with EVs (in the absence of antiviral antibodies) and thus might be an enterovirus target in vivo and serve as a virus reservoir in blood. "
[Show abstract] [Hide abstract]
ABSTRACT: Coxsackie B viruses (CVBs) and echoviruses (EVs) form the Human Enterovirus-B (HEV-B) species within the family Picornaviridae. HEV-B infections are widespread and generally cause mild disease; however, severe infections occur and HEV-B are associated with various chronic diseases such as cardiomyopathy and type 1 diabetes. Dendritic cells (DCs) are the professional antigen-presenting cells of our immune system and initiate and control immune responses to invading pathogens, yet also maintain tolerance to self-antigens. We previously reported that EVs, but not CVBs, can productively infect in vitro generated monocyte-derived DCs. The interactions between HEV-B and human myeloid DCs (mDCs) freshly isolated from blood, however, remain unknown. Here, we studied the susceptibility and responses of BDCA1(+) mDC to HEV-B species and found that these mDC are susceptible to EV, but not CVB infection. Productive EV7 infection resulted in massive, rapid cell death without DC activation. Contrary, EV1 infection, which resulted in lower virus input at the same MOI, resulted in DC activation as observed by production of type I interferon-stimulated genes (ISGs), upregulation of co-stimulatory and co-inhibitory molecules (CD80, CD86, PDL1) and production of IL-6 and TNF-α, with a relative moderate decrease in cell viability. EV1-induced ISG expression depended on virus replication. CVB infection did not affect DC viability and resulted in poor induction of ISGs and CD80 induction in part of the donors. These data show for the first time the interaction between HEV-B species and BDCA1(+) mDCs isolated freshly from blood. Our data indicate that different HEV-B species can influence DC homeostasis in various ways, possibly contributing to HEV-B associated pathology.
PLoS ONE 04/2013; 8(4):e62502. DOI:10.1371/journal.pone.0062502 · 3.23 Impact Factor
Available from: Goffard Anne
- "The present study demonstrates that CV- B4 in ADE conditions can stimulate the synthesis of IFNa by differenciated-THP-1 cells. Although the level of IFNa in the supernatant fluid was low in the THP-1 model, the antibody-dependent enhancement of CV-B4 infection in this monocyte-like cell line associated with the synthesis of IFNa is in agreement with previous reports demonstrating that monocytes were the major target of the virus and were IFN-a-producing cells among PBMC in response to CV-B4eIgG complexes  . This study shows that PMA-activated THP-1 cells can be considered as a model to investigate further the mechanisms of the infection with CV- B4 that is enhanced with antibodies. "
[Show abstract] [Hide abstract]
ABSTRACT: Coxsackievirus B4 (CV-B4), in presence of antibodies and through a specific viral receptor CAR and Fcγ receptors II and III, can infect monocytes which results in interferon-α synthesis. The antibody-dependent enhancement of CV-B4 infection in the human monocytic-like THP-1 cell line has been investigated. The preincubation of CV-B4 with human plasma or human polyvalent immunoglobulins enhanced the infection of phorbol-myristate-acetate (PMA)-activated THP-1 cell cultures. CV-B4 replicated in these cells as demonstrated by the intracellular detection of infectious particles, viral protein VP1 (immunofluorescence), positive and negative viral RNA (RT-PCR). The viability of infected and control cell cultures was not different up to 20 days post-infection. Activated cell cultures inoculated with CV-B4 harbored intracellular RNA up to 14 days post-infection and produced IFNα that was detected by intracellular immunofluorescence staining as soon as 4 h post-infection with a maximum at 48 h post-infection and by RT-PCR all along the experiment. Together, these data demonstrate that PMA-activated THP-1 cells can be infected with CV-B4, can produce IFNα as a result of interactions between the virus, antibodies and specific receptors. This cellular model can be used to investigate further the mechanism and the result of the antibody-dependent enhancement of CV-B4 infection.
Microbes and Infection 10/2012; 15(1). DOI:10.1016/j.micinf.2012.10.005 · 2.86 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.