Dengue mouse models for evaluating pathogenesis and countermeasures

Chen, Rita E.; Diamond, Michael S.

doi:10.1016/j.coviro.2020.09.001

Cited by 35 publications

(34 citation statements)

References 108 publications

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“…Unfortunately, mice are resistant to YFV infection and show limited susceptibility for YF17D. Among many other factors hampering flavivirus infection [ 47 , 48 ], productive YF17D replication and hence vaccination is restricted by vigorous type I IFN responses in mice [ 21 ]. Therefore, also YF17D-derived vaccines are mainly assessed in immune-deficient mice missing key antiviral IFN-α/β receptors.…”

Section: Discussionmentioning

confidence: 99%

Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice

Boudewijns

Sánchez-Felipe

et al. 2021

Emerging Microbes & Infections

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The live-attenuated yellow fever 17D (YF17D) vaccine is one of the most efficacious human vaccines and also employed as a vector for novel vaccines. However, in the lack of appropriate immunocompetent small animal models, mechanistic insight in YF17D-induced protective immunity remains limited. To better understand YF17D vaccination and to identify a suitable mouse model, we evaluated the immunogenicity and protective efficacy of YF17D in five complementary mouse models, i.e. wild-type (WT) BALB/c, C57BL/6, IFN-α/β receptor ( IFNAR -/- ) deficient mice, and in WT mice in which type I IFN signalling was temporally ablated by an IFNAR blocking (MAR-1) antibody. Alike in IFNAR -/- mice, YF17D induced in either WT mice strong humoral immune responses dominated by IgG2a/c isotype (Th1 type) antibodies, yet only when IFNAR was blocked. Vigorous cellular immunity characterized by CD4 + T-cells producing IFN-γ and TNF-α were mounted in MAR-1 treated C57BL/6 and in IFNAR -/- mice. Surprisingly, vaccine-induced protection was largely mouse model dependent. Full protection against lethal intracranial challenge and a massive reduction of virus loads was conferred already by a minimal dose of 2 PFU YF17D in BALB/c and IFNAR -/- mice, but not in C57BL/6 mice. Correlation analysis of infection outcome with pre-challenge immunological markers indicates that YFV-specific IgG might suffice for protection, even in the absence of detectable levels of neutralizing antibodies. Finally, we propose that, in addition to IFNAR -/- mice, C57BL/6 mice with temporally blocked IFN-α/β receptors represent a promising immunocompetent mouse model for the study of YF17D-induced immunity and evaluation of YF17D-derived vaccines.

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Section: Discussionmentioning

confidence: 99%

Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice

Boudewijns

Sánchez-Felipe

et al. 2021

Emerging Microbes & Infections

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“…A major limitation in understanding the mechanisms underlining those issues is the lack of an immunocompetent mouse experimental model that sustains virus replication and present dengue clinical signs after systemic inoculation. Since DENV nonstructural proteins 5 (NS5) and 2B/3 (NS2B/3) degrade human, but not mouse STAT2 and STING, respectively, adult mouse animal models poorly reproduce the dengue infection, unless type I and II interferon receptors are knocked out (IFNAR/IFNGR-/-Ag129) [ 26 , 27 , 28 ]. Therefore, it is still unclear whether systemic thrombo-inflammatory responses might converge with endothelial injury caused by DENV.…”

Section: Introductionmentioning

confidence: 99%

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

et al. 2021

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Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus (DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa) in the large majority of samples from a dengue cohort (n = 70), irrespective of severity of clinical symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact system is frequently triggered during the course of infection. Using two pathogenic arboviruses, DENV or Zika virus (ZIKV), we then asked whether exogenous BK could influence the outcome of infection of human brain microvascular endothelial cells (HBMECs). Unlike the unresponsive phenotype of Zika-infected HBMECs, we found that BK, acting via B2R, vigorously stimulated DENV-2 replication by reverting nitric oxide-driven apoptosis of endothelial cells. Using the mouse model of cerebral dengue infection, we next demonstrated that B2R targeting by icatibant decreased viral load in brain tissues. In summary, our study suggests that contact/KKS activation followed by BK-induced enhancement of DENV replication in the endothelium may underlie microvascular pathology in dengue.

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“…Although wild-type mice and other rodents (e.g., guinea pigs, hamsters, and rats) are resistant to most arboviral infection and disease, immunodeficient mouse models for viral infection have evolved with increasing success during the last two decades [ 43 , 44 , 45 , 46 , 47 , 48 ]. Mice that lack both the type I and II IFN receptors, AG129 mice (double Knockout for type I & II receptors -IFN-α/β and -γ), are now being used extensively in arbovirus studies [ 37 , 40 , 46 , 49 , 50 , 51 , 52 ]. Here, we inoculated juvenile AG129 mice with OROV through intraperitoneal (IP) injection, and analysed both survival rates and blood viremia kinetics ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus Mosquitoes Competence to Oropouche virus Infection

Mendonça¹,

Rocha

Ferreira

et al. 2021

Viruses

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The emergence of new human viral pathogens and re-emergence of several diseases are of particular concern in the last decades. Oropouche orthobunyavirus (OROV) is an arbovirus endemic to South and Central America tropical regions, responsible to several epidemic events in the last decades. There is little information regarding the ability of OROV to be transmitted by urban/peri-urban mosquitoes, which has limited the predictability of the emergence of permanent urban transmission cycles. Here, we evaluated the ability of OROV to infect, replicate, and be transmitted by three anthropophilic and urban species of mosquitoes, Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. We show that OROV is able to infect and efficiently replicate when systemically injected in all three species tested, but not when orally ingested. Moreover, we find that, once OROV replication has occurred in the mosquito body, all three species were able to transmit the virus to immunocompromised mice during blood feeding. These data provide evidence that OROV is restricted by the midgut barrier of three major urban mosquito species, but, if this restriction is overcome, could be efficiently transmitted to vertebrate hosts. This poses a great risk for the emergence of permanent urban cycles and geographic expansion of OROV to other continents.

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Dengue mouse models for evaluating pathogenesis and countermeasures

Cited by 35 publications

References 108 publications

Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice

Comparing immunogenicity and protective efficacy of the yellow fever 17D vaccine in mice

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

Evaluation of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus Mosquitoes Competence to Oropouche virus Infection

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