Prior Dengue Virus Infection Is Associated With Increased Viral Load in Patients Infected With Dengue but Not Zika Virus

Abstract To evaluate potential enhancement of Zika virus (ZIKV) infection among patients with prior dengue virus (DENV) infection, we compared loads of viral RNA among patients infected with ZIKV (n = 1070), DENV-2 (n = 312), or DENV-3 (n = 260). Compared to patients without prior DENV infection, patients with prior DENV infection had significantly higher mean loads of viral RNA if infected with DENV-2 (10.6 vs 11.6 log10 GCE/mL, respectively; t test, P < .0001) or DENV-3 (10.3 vs 10.9 log10 GCE/mL; P < .0001), but not ZIKV (4.7 vs 4.7 log10 GCE/mL; P = .959). These findings provide evidence against in vivo enhancement of ZIKV by anti-DENV antibodies.

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Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

Journal of Clinical Microbiology ◽

10.1128/jcm.01504-17 ◽

2017 ◽

Vol 56 (3) ◽

Cited By ~ 16

Author(s):

Lakshmanane Premkumar ◽

Matthew Collins ◽

Stephen Graham ◽

Guei-Jiun Alice Liou ◽

Cesar A. Lopez ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Envelope Protein ◽

Population Level ◽

Denv Infection ◽

Cross Reactivity ◽

Protein Antigens ◽

Zikv Infection ◽

Serological Tests

ABSTRACT Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.

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Congenital abnormalities associated with Zika virus infection–Dengue as potential co-factor? A systematic review

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008984 ◽

2021 ◽

Vol 15 (1) ◽

pp. e0008984

Author(s):

Stephanie Petzold ◽

Nisreen Agbaria ◽

Andreas Deckert ◽

Peter Dambach ◽

Volker Winkler ◽

...

Keyword(s):

Systematic Review ◽

Virus Infection ◽

Dengue Virus ◽

Protective Effect ◽

Zika Virus ◽

Congenital Abnormalities ◽

Denv Infection ◽

Current Evidence ◽

Geographic Variability ◽

Zikv Infection

Zika virus (ZIKV) emerged in Brazil during 2013–2014 causing an epidemic of previously unknown congenital abnormalities. The frequency of severe congenital abnormalities after maternal ZIKV infection revealed an unexplained geographic variability, especially between the Northeast and the rest of Brazil. Several reasons for this variability have been discussed. Prior immunity against DENV, that affects ZIKV seems to be the most likely explanation. Here we summarise the current evidence regarding the prominent co-factor to potentially explain the geographic variability. This systematic review followed the PRISMA guidelines. The search was conducted up to May 15th, 2020, focussing on immunological interactions from Zika virus with previous Dengue virus infections as potential teratogenic effect for the foetus. Eight out of 339 screened studies reported on the association between ZIKV, prior Dengue virus infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. Prior DENV infection was associated with enhancement for ZIKV infection and increased neurovirulence in one included in vitro study only. Interestingly, the seven in vivo studies exhibited a heterogeneous picture with three studies showing a protective effect of prior DENV infections and others no effect at all. According to several studies, socio-economic factors are associated with increased risk for microcephaly. Very few studies addressed the question of unexplained variability of infection-related microcephaly. Many studies focussed on ADE as mechanism without measuring microcephaly as endpoint. Interestingly, three of the included studies reported a protective effect of prior DENV infection against microcephaly. This systematic review strengthens the hypothesis that immune priming after recent DENV infection is the crucial factor for determining protection or enhancement activity. It is of high importance that the currently ongoing prospective studies include a harmonized assessment of the potential candidate co-factors.

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Zika virus infection in a traveller returning from the Maldives, June 2015

Eurosurveillance ◽

10.2807/1560-7917.es.2016.21.2.30107 ◽

2016 ◽

Vol 21 (2) ◽

Cited By ~ 50

Author(s):

Essi Marjana Korhonen ◽

Eili Huhtamo ◽

Teemu Smura ◽

Hannimari Kallio-Kokko ◽

Markku Raassina ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Denv Infection ◽

Distribution Range ◽

Rt Pcr ◽

Zikv Infection ◽

Igm Antibodies ◽

Zika Virus Infection

We report a Zika virus (ZIKV) infection in a patient with fever and rash after returning to Finland from Maldives, June 2015. The patient had dengue virus (DENV) IgG and IgM antibodies but pan-flavivirus RT-PCR and subsequent sequencing showed presence of ZIKV RNA in urine. Recent association of ZIKV with microcephaly highlights the need for laboratory differentiation of ZIKV from DENV infection and the circulation of ZIKV in areas outside its currently known distribution range.

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Faculty Opinions recommendation of Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727533754.793531093 ◽

2017 ◽

Author(s):

Scott Halstead

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Dengue Virus Infection

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Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

Mediators of Inflammation ◽

10.1155/2020/9527147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Yuyi Huang ◽

Yujie Wang ◽

Shuhui Meng ◽

Zhuohang Chen ◽

Haifan Kong ◽

...

Keyword(s):

Virus Infection ◽

Cell Line ◽

Zika Virus ◽

Fetal Brain ◽

Host Immunity ◽

Type I ◽

Type I Ifn ◽

Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

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Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests

Clinical Infectious Diseases ◽

10.1093/cid/cix672 ◽

2017 ◽

Vol 65 (11) ◽

pp. 1829-1836 ◽

Cited By ~ 40

Author(s):

Wen-Yang Tsai ◽

Han Ha Youn ◽

Carlos Brites ◽

Jih-Jin Tsai ◽

Jasmine Tyson ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Dengue Virus Infection ◽

Serological Tests ◽

Zika Virus Infection

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Animal Models of Zika Virus Infection during Pregnancy

Viruses ◽

10.3390/v10110598 ◽

2018 ◽

Vol 10 (11) ◽

pp. 598 ◽

Cited By ~ 29

Author(s):

Elizabeth Caine ◽

Brett Jagger ◽

Michael Diamond

Keyword(s):

Animal Models ◽

Virus Infection ◽

Zika Virus ◽

Reproductive Tract ◽

Congenital Abnormalities ◽

Tissue Tropism ◽

Zikv Infection ◽

In Vivo Models ◽

Sexually Transmitted

Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

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Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection

Journal of Virology ◽

10.1128/jvi.01096-16 ◽

2016 ◽

Vol 90 (24) ◽

pp. 11122-11131 ◽

Cited By ~ 9

Author(s):

Meihui Xu ◽

Roland Züst ◽

Ying Xiu Toh ◽

Jennifer M. Pfaff ◽

Kristen M. Kahle ◽

...

Keyword(s):

Virus Infection ◽

Antibody Response ◽

Dengue Virus ◽

Secondary Infection ◽

Immune Memory ◽

Protective Capacity ◽

Dengue Virus Infection ◽

Immune Correlates

ABSTRACT Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo . IMPORTANCE Antibodies can protect from symptomatic dengue virus infection. However, it is not easy to assess which classes of antibodies provide protection because in vitro assays are not always predictive of in vivo protection. During a repeat infection, dengue virus-specific immune memory cells are reactivated and large amounts of antibodies are produced. By studying antibodies cloned from patients with heterologous secondary infection, we tested the protective value of the serotype-cross-reactive “recall” or “anamnestic” response. We found that results from in vitro neutralization assays did not always correlate with the ability of the antibodies to reduce viremia in a mouse model. In addition, a decrease of viremia in mice did not necessarily improve survival. The most protective antibodies were stable at pH 5, suggesting that antibody binding in the endosomes, after the antibody-virus complex is internalized, might be important to block virus spread in the organism.

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