Special Issue "6th Pan-American Dengue Research Network Meeting"

A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (30 September 2018).

Special Issue Editors

Assoc. Prof. Nikolaos Vasilakis
E-Mail Website
Guest Editor
Department of Pathology and Center of Biodefense and Emerging Infectious Diseases; Center for Tropical Diseases; and Institute for Human Infection and Immunity University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0609, USA
Interests: basic research on evolution and pathogenesis of arthropod-borne viruses; quasispecies in transmission dynamics and emergence; and discovery and characterization of novel/new viruses
Special Issues and Collections in MDPI journals
Dr. Carlos A. Sariol
E-Mail Website1 Website2
Guest Editor
Unit of Comparative Medicine, Caribbean Primate Research Center, Department of Microbiology and Medical Zoology, Department of Internal Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico, USA
Interests: basic research on flavivirus interactions at molecular level and pathogenesis; vaccine development and characterization of novel viruses in non human primate model; also interested and actively involved in clinical trials for several diseases including flavivirus vaccines

Special Issue Information

Dear Colleagues,

The Pan-American Dengue Research Network Meeting (http://www.pandenguenet.org) is an initiative to gather researchers across the Americas every two years to discuss their recent advancements in the field, communicate this information to the scientific community in the region, foster collaborations among groups, and discuss future research strategies that will further strengthen the field. During these meetings, cutting-edge topics on dengue field are presented and discussed. One of the main objectives of this application is to guarantee the participation of many graduate students and junior investigators from Latin American and Caribbean regions, which have been usually underrepresented in science. The scientific meeting to be held for the first time in the US and undoubtedly will make an important contribution to supporting and broadening the impact of research on dengue throughout the hemisphere. Additionally, for this meeting the scientific scope will be expanded to cover Zika, chikungunya and Mayaro, arboviroses that have recently re-emerged in the Americas with devastating effects for human public health. Lastly, we will celebrate and honor the contributions of Robert Tesh and Hilda Guzman to arbovirology, both of whom have recently retired after 30 years as curators of the World Reference Collection of Emerging Viruses and Arboviruses (WRCEVA). The collection of reviews and original research papers in this Special Issue is intended to summarize and showcase current research on arboviruses by investigators from throughout the Americas.

Assoc. Prof. Nikolaos Vasilakis
Dr. Carlos A. Sariol
Guest Editors

Manuscript Submission Information

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Keywords

  • Dengue
  • Zika
  • Chikungunya
  • Yellow fever
  • Mayaro
  • vaccine
  • pathogenesis
  • immunology
  • virology

Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle
Molecular Epidemiology of Dengue in Panama: 25 Years of Circulation
Viruses 2019, 11(8), 764; https://doi.org/10.3390/v11080764 - 20 Aug 2019
Abstract
Dengue virus (DENV) is the most prevalent arbovirus in terms of human public health importance globally. In addition to DENV epidemiological surveillance, genomic surveillance may help investigators understand the epidemiological dynamics, geographic distribution, and temporal patterns of DENV circulation. Herein, we aimed to [...] Read more.
Dengue virus (DENV) is the most prevalent arbovirus in terms of human public health importance globally. In addition to DENV epidemiological surveillance, genomic surveillance may help investigators understand the epidemiological dynamics, geographic distribution, and temporal patterns of DENV circulation. Herein, we aimed to reconstruct the molecular epidemiology and phylogeny of DENV in Panama to connect the epidemiological history of DENV dispersal and circulation in Latin America. We retrospectively analyzed the epidemiological data obtained during 25 years of DENV surveillance in Panama. DENV was reintroduced in Panama in 1993 after a 35 year absence of autochthonous transmission. The increase in the number of total dengue cases has been accompanied by an increase in severe and fatal cases, with the highest case fatality rate recorded in 2011. All four serotypes were detected in Panama, which is characterized by serotype replacement and/or co-circulation of multiple serotypes. Phylogenetic analysis of datasets collected from envelope (E) gene sequences obtained from viruses isolated from human sera demonstrated that circulating viruses were highly diverse and clustered in distinct clades, with co-circulation of clades from the same genotype. Our analyses also suggest that Panamanian strains were related to viruses from different regions of the Americas, suggesting a continuous exchange of viruses within the Americas. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques
Viruses 2018, 10(11), 661; https://doi.org/10.3390/v10110661 - 21 Nov 2018
Cited by 4
Abstract
To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with [...] Read more.
To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with 5.0 log10 focus-forming units (FFU) of DNA clone-derived ZIKV strain FSS13025 (Asian lineage, Cambodia, 2010). Following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health monitoring, and were exposed to Ae. aegypti at specified time points. All four animals developed viremia, which peaked 3–4 days post-infection at a maximum value of 6.9 log10 genome copies/mL. No virus was detected in urine, tears, or saliva. Infection by ZIKV caused minimal overt disease: serum biochemistry and CBC values largely fell within the normal ranges, and cytokine elevations were minimal. Strikingly, the minimally colonized population of Ae. aegypti exposed to viremic animals demonstrated a maximum infection rate of 26% during peak viremia, with two of the four macaques failing to infect a single mosquito at any time point. These data indicate that cynomolgus macaques may be an effective model for ZIKV infection of humans and highlights the relative refractoriness of Ae. aegypti for ZIKV infection at the levels of viremia observed. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Willingness to Participate and Associated Factors in a Zika Vaccine Trial in Indonesia: A Cross-Sectional Study
Viruses 2018, 10(11), 648; https://doi.org/10.3390/v10110648 - 18 Nov 2018
Cited by 3
Abstract
One of the crucial steps during trials for Zika and other vaccines is to recruit participants and to understand how participants’ attitudes and sociodemographic characteristics affect willingness to participate (WTP). This study was conducted to assess WTP, its explanatory variables, and the impact [...] Read more.
One of the crucial steps during trials for Zika and other vaccines is to recruit participants and to understand how participants’ attitudes and sociodemographic characteristics affect willingness to participate (WTP). This study was conducted to assess WTP, its explanatory variables, and the impact of financial compensation on WTP in Indonesia. A health facility-based cross-sectional study was conducted in eleven regencies in the Aceh and West Sumatra provinces of Indonesia. Participants were recruited via a convenience sampling method and were interviewed. The associations between explanatory variables and WTP were assessed using a two-step logistic regression analysis. A total of 1,102 parents were approached, and of these 956 (86.8%) completed the interview and were included in analysis. Of those, 144 (15.1%) were willing to participate in a Zika vaccine trial without a financial compensation. In the multivariate analysis, WTP was tied to an age of more than 50 years old, compared to 20–29 years (odds ratio (OR): 5.0; 95% confidence interval (CI): 2.37–10.53), to being female (OR: 2.20; 95% CI: 1.11–4.37), and to having heard about Zika (OR: 2.41; 95% CI: 1.59–3.65). Participants’ WTP increased gradually with higher financial compensation. The rate of WTP increased to 62.3% at the highest offer (US$ 350.4), and those who were still unwilling to participate (37.7%) had a poorer attitude towards childhood vaccination. This study highlights that pre-existing knowledge about Zika and attitudes towards childhood vaccination are important in determining community members being willing to participate in a vaccine trial. Financial incentives are still an important factor to enhance participant recruitment during a vaccine trial. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Human Fetal Astrocytes Infected with Zika Virus Exhibit Delayed Apoptosis and Resistance to Interferon: Implications for Persistence
Viruses 2018, 10(11), 646; https://doi.org/10.3390/v10110646 - 17 Nov 2018
Cited by 10
Abstract
Zika virus (ZIKV) infection and persistence during pregnancy can lead to microcephaly and other fetal neurological disorders collectively known as Congenital Zika Syndrome. The immunological and virological events that contribute to the establishment of persistent ZIKV infection in humans are unclear though. Here [...] Read more.
Zika virus (ZIKV) infection and persistence during pregnancy can lead to microcephaly and other fetal neurological disorders collectively known as Congenital Zika Syndrome. The immunological and virological events that contribute to the establishment of persistent ZIKV infection in humans are unclear though. Here we show that human fetal astrocytes (HFAs), the most abundant cell type in the central nervous system, become persistently infected with ZIKV resulting in continuous viral shedding for at least one month; a process that is facilitated by TIM/TAM receptors. HFAs are relatively resistant to ZIKV-induced apoptosis, a factor that may be important for chronic infection of these cells. Once infection was established, interferon treatment did not reduce virus replication. Moreover, the fact that the innate immune system was highly activated in persistently infected HFAs indicates that the virus can thrive in the presence of a sustained antiviral response. RNAseq analyses of persistently infected cells revealed that ZIKV alters host gene expression in a manner that could affect developmental processes. Conversely, data from sequencing of ZIKV genomes in persistently infected HFAs suggest that adaptive mutations were not required for establishing chronic infection. Based on these results, we postulate that HFAs are reservoirs for ZIKV in the fetal brain and that moderate apoptosis combined with inefficient antiviral response from these cells may contribute to the establishment of chronic brain infection associated with the ZIKV neurodevelopmental abnormalities. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Following in the Footsteps of the Chikungunya Virus in Brazil: The First Autochthonous Cases in Amapá in 2014 and Its Emergence in Rio de Janeiro during 2016
Viruses 2018, 10(11), 623; https://doi.org/10.3390/v10110623 - 12 Nov 2018
Cited by 1
Abstract
Currently, Brazil lives a triple arboviruses epidemic (DENV, ZIKV and CHIKV) making the differential diagnosis difficult for health professionals. Here, we aimed to investigate chikungunya cases and the possible occurrence of co-infections during the epidemic in Amapá (AP) that started in 2014 when [...] Read more.
Currently, Brazil lives a triple arboviruses epidemic (DENV, ZIKV and CHIKV) making the differential diagnosis difficult for health professionals. Here, we aimed to investigate chikungunya cases and the possible occurrence of co-infections during the epidemic in Amapá (AP) that started in 2014 when the first autochthonous cases were reported and in Rio de Janeiro (RJ) in 2016. We further performed molecular characterization and genotyping of representative strains. In AP, 51.4% of the suspected cases were confirmed for CHIKV, 71.0% (76/107). Of those, 24 co-infections by CHIKV/DENV, two by CHIKV/DENV-1, and two by CHIKV/DENV-4 were observed. In RJ, 76.9% of the suspected cases were confirmed for CHIKV and co-infections by CHIKV/DENV (n = 8) and by CHIKV/ZIKV (n = 17) were observed. Overall, fever, arthralgia, myalgia, prostration, edema, exanthema, conjunctival hyperemia, lower back pain, dizziness, nausea, retroorbital pain, and anorexia were the predominating chikungunya clinical symptoms described. All strains analyzed from AP belonged to the Asian genotype and no amino acid changes were observed. In RJ, the East-Central-South-African genotype (ECSA) circulation was demonstrated and no E1-A226V mutation was observed. Despite this, an E1-V156A substitution was characterized in two samples and for the first time, the E1-K211T mutation was reported in all samples analyzed. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Improved Immune Responses Against Zika Virus After Sequential Dengue and Zika Virus Infection in Humans
Viruses 2018, 10(9), 480; https://doi.org/10.3390/v10090480 - 07 Sep 2018
Cited by 8
Abstract
The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. [...] Read more.
The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. To determine the role of DENV preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against ZIKV in donors with or without previous DENV infection. Using peripheral blood mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS) proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors in comparison with DENV-naïve donors. Strikingly, the potential for antibody-mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Colonized Sabethes cyaneus, a Sylvatic New World Mosquito Species, Shows a Low Vector Competence for Zika Virus Relative to Aedes aegypti
Viruses 2018, 10(8), 434; https://doi.org/10.3390/v10080434 - 16 Aug 2018
Cited by 3
Abstract
The introduction of Zika virus (ZIKV) to the Americas raised concern that the virus would spill back from human transmission, perpetuated by Aedes aegypti, into a sylvatic cycle maintained in wildlife and forest-living mosquitoes. In the Americas, Sabethes species are vectors of [...] Read more.
The introduction of Zika virus (ZIKV) to the Americas raised concern that the virus would spill back from human transmission, perpetuated by Aedes aegypti, into a sylvatic cycle maintained in wildlife and forest-living mosquitoes. In the Americas, Sabethes species are vectors of sylvatic yellow fever virus (YFV) and are therefore candidate vectors of a sylvatic ZIKV cycle. To test the potential of Sabethes cyaneus to transmit ZIKV, Sa. cyaneus and Ae. aegypti were fed on A129 mice one or two days post-infection (dpi) with a ZIKV isolate from Mexico. Sa. cyaneus were sampled at 3, 4, 5, 7, 14, and 21 days post-feeding (dpf) and Ae. aegypti were sampled at 14 and 21 dpf. ZIKV was quantified in mosquito bodies, legs, and saliva to measure infection, dissemination, and potential transmission, respectively. Of 69 Sa. cyaneus that fed, ZIKV was detected in only one, in all body compartments, at 21 dpf. In contrast, at 14 dpf 100% of 20 Ae. aegypti that fed on mice at 2 dpi were infected and 70% had virus in saliva. These data demonstrate that Sa. cyaneus is a competent vector for ZIKV, albeit much less competent than Ae. aegypti. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
Open AccessArticle
NS1 Antigenemia and Viraemia Load: Potential Markers of Progression to Dengue Fatal Outcome?
Viruses 2018, 10(6), 326; https://doi.org/10.3390/v10060326 - 14 Jun 2018
Cited by 1
Abstract
Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the secreted nonstructural protein 1 (NS1) may be associated with a more severe disease. We aimed to characterize the [...] Read more.
Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the secreted nonstructural protein 1 (NS1) may be associated with a more severe disease. We aimed to characterize the NS1 antigenemia and viremia in dengue fatal and non-fatal cases, as potential markers of progression to a fatal outcome. NS1 antigenemia and viremia were determined in Brazilian dengue fatal cases (n = 40) and non-fatal cases (n = 40), representative of the four dengue virus (DENV) serotypes. Overall, the fatal cases presented higher NS1 levels and viremia. Moreover, the fatal cases from secondary infections showed significantly higher NS1 levels than the non-fatal ones. Here, irrespective of the disease outcome, DENV-1 cases presented higher NS1 levels than the other serotypes. However, DENV-2 and DENV-4 fatal cases had higher NS1 antigenemia than the non-fatal cases with the same serotype. The viremia in the fatal cases was higher than in the non-fatal ones, with DENV-3 and DENV-4 presenting higher viral loads. Viral components, such as NS1 and viral RNA, may be factors influencing the disease outcome. However, the host immune status, comorbidities, and access to adequate medical support cannot be ruled out as interfering in the disease outcome. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Molecular and Clinical Characterization of Chikungunya Virus Infections in Southeast Mexico
Viruses 2018, 10(5), 248; https://doi.org/10.3390/v10050248 - 09 May 2018
Cited by 3
Abstract
Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there is no detailed information. The aim of this study was to perform a full description of [...] Read more.
Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there is no detailed information. The aim of this study was to perform a full description of the clinical features in confirmed Chikungunya-infected patients and describe the molecular epidemiology of CHIKV. We evaluated febrile patients who sought medical assistance in Tapachula, Chiapas, Mexico, from June through July 2015. Infection was confirmed with molecular and serological methods. Viruses were isolated and the E1 gene was sequenced. Phylogeny reconstruction was inferred using maximum-likelihood and maximum clade credibility approaches. We studied 52 patients with confirmed CHIKV infection. They were more likely to have wrist, metacarpophalangeal, and knee arthralgia. Two combinations of clinical features were obtained to differentiate between Chikungunya fever and acute undifferentiated febrile illness. We obtained 10 CHIKV E1 sequences that grouped with the Asian lineage. Seven strains diverged from the formerly reported. Patients infected with the divergent CHIKV strains showed a broader spectrum of clinical manifestations. We defined the complete clinical features of Chikungunya fever in patients from Southeastern Mexico. Our results demonstrate co-circulation of different CHIKV strains in the state of Chiapas. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Increased Levels of Txa2 Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue
Viruses 2018, 10(3), 104; https://doi.org/10.3390/v10030104 - 28 Feb 2018
Abstract
The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during [...] Read more.
The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Review

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Open AccessReview
Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)
Viruses 2019, 11(5), 477; https://doi.org/10.3390/v11050477 - 25 May 2019
Abstract
Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and [...] Read more.
Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA). Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessReview
Exploiting the Legacy of the Arbovirus Hunters
Viruses 2019, 11(5), 471; https://doi.org/10.3390/v11050471 - 23 May 2019
Abstract
In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of [...] Read more.
In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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