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Fulltext Viral Protein Accumulation of Zika Virus Variants Links with Regulation of Innate Immunity for Differential Control of Viral Replication, Spread, and Response to Interferon

Lu AY, Gustin A, Newhouse D, Gale M

J Virol, 2023 May 31;97(5):e0198222.
PMID: 37162358 DOI: 10.1128/jvi.01982-22

Asian lineage Zika virus (ZIKV) strains emerged globally, causing outbreaks linked with critical clinical disease outcomes unless the virus is effectively restricted by host immunity. We have previously shown that retinoic acid-inducible gene-I (RIG-I) senses ZIKV to trigger innate immunity to direct interferon (IFN) production and antiviral responses that can control ZIKV infection. However, ZIKV proteins have been demonstrated to antagonize IFN. Here, we conducted in vitro analyses to assess how divergent prototypic ZIKV variants differ in virologic properties, innate immune regulation, and infection outcome. We comparatively assessed African lineage ZIKV/Dakar/1984/ArD41519 (ZIKV/Dakar) and Asian lineage ZIKV/Malaysia/1966/P6740 (ZIKV/Malaysia) in a human epithelial cell infection model. De novo viral sequence determination identified amino acid changes within the ZIKV/Dakar genome compared to ZIKV/Malaysia. Viral growth analyses revealed that ZIKV/Malaysia accumulated viral proteins and genome copies earlier and to higher levels than ZIKV/Dakar. Both ZIKV strains activated RIG-I/IFN regulatory factor (IRF3) and NF-κB pathways to induce inflammatory cytokine expression and types I and III IFNs. However, ZIKV/Malaysia, but not ZIKV/Dakar, potently blocked downstream IFN signaling. Remarkably, ZIKV/Dakar protein accumulation and genome replication were rescued in RIG-I knockout (KO) cells late in acute infection, resulting in ZIKV/Dakar-mediated blockade of IFN signaling. We found that RIG-I signaling specifically restricts viral protein accumulation late in acute infection where early accumulation of viral proteins in infected cells confers enhanced ability to limit IFN signaling, promoting viral replication and spread. Our results demonstrate that RIG-I-mediated innate immune signaling imparts restriction of ZIKV protein accumulation, which permits IFN signaling and antiviral actions controlling ZIKV infection. IMPORTANCE ZIKV isolates are classified under African or Asian lineages. Infection with emerging Asian lineage-derived ZIKV strains is associated with increased incidence of neurological symptoms that were not previously reported during infection with African or preemergent Asian lineage viruses. In this study, we utilized in vitro models to compare the virologic properties of and innate immune responses to two prototypic ZIKV strains from distinct lineages: African lineage ZIKV/Dakar and Asian lineage ZIKV/Malaysia. Compared to ZIKV/Dakar, ZIKV/Malaysia accumulates viral proteins earlier, replicates to higher levels, and robustly blocks IFN signaling during acute infection. Early accumulation of ZIKV/Malaysia NS5 protein confers enhanced ability to antagonize IFN signaling, dampening innate immune responses to promote viral spread. Our data identify the kinetics of viral protein accumulation as a major regulator of host innate immunity, influencing host-mediated control of ZIKV replication and spread. Importantly, these findings provide a novel framework for evaluating the virulence of emerging variants.

Matched MeSH terms: Zika Virus Infection*
Fulltext Knowledge and attitude towards pregnancy-related issues of Zika virus infection among general practitioners in Indonesia

Harapan H, Rajamoorthy Y, Utomo PS, Anwar S, Setiawan AM, Alleta A, et al.

BMC Infect Dis, 2019 Aug 06;19(1):693.
PMID: 31387537 DOI: 10.1186/s12879-019-4297-4

BACKGROUND: The aim of this study was to assess the knowledge and attitudes towards pregnancy-related issues of Zika virus (ZIKV) infection among general practitioners (GPs), a frontline healthcare worker group, in Indonesia.
METHODS: A cross-sectional, online survey assessing knowledge and attitudes towards ZIKV infection on multiple-item scales was sent to GPs in the Sumatra and Java islands of Indonesia. The associations between independent factors and either knowledge or attitude were assessed with logistic regressions. The correlation and association between knowledge and attitude were estimated.
RESULTS: We included 457 (53.7%) out of 850 responses in the analysis. Among these, 304 (66.5%) and 111 (24.2%) respondents had a good knowledge and attitude, respectively. No demographic, workplace, professional development, or experiential characteristics related to ZIKV infection were associated with knowledge. In the multivariate analysis, only contact experience was associated with attitude. There was a significant, positive correlation between knowledge and attitude scores.
CONCLUSIONS: Although knowledge of pregnancy-related complications of ZIKV infection is relatively high among GPs in Indonesia, more than 75% of them had a poor attitude towards pregnancy-related issues of Zika. Strategies for enhancing the capacity of GPs to develop positive attitudes and respond to ZIKV infection are needed.

Matched MeSH terms: Zika Virus Infection/etiology*
Community acceptance and willingness-to-pay for a hypothetical Zika vaccine: A cross-sectional study in Indonesia

Harapan H, Mudatsir M, Yufika A, Nawawi Y, Wahyuniati N, Anwar S, et al.

Vaccine, 2019 03 07;37(11):1398-1406.
PMID: 30739794 DOI: 10.1016/j.vaccine.2019.01.062

BACKGROUND: Understanding people's perceptions of the economic benefits of a potential Zika vaccine (ZV) is critical to accelerating its introduction into either public sector programs or private market. The aim of this study was to assess the acceptance and willingness-to-pay (WTP) for a hypothetical ZV and the associated explanatory variables in Indonesia.
METHODS: We conducted a health facility-based cross-sectional study in Aceh and West Sumatra province from 1 February to 13 June 2018. Patients who visited outpatient departments, have had children or were expecting their first child, were approached and interviewed to collect information on acceptance, WTP, demographic and socio-economic variables and attitudes towards childhood vaccines. Associations of explanatory variables influencing acceptance and WTP were assessed using logistic regression and linear regression analysis, respectively.
RESULTS: In total, 956 respondents were included in the final analysis of acceptance, of whom 338 (35.3%) expressed their WTP. We found that 757 (79.1%) of the respondents were likely to be vaccinated and to recommend their partner to be vaccinated. Higher educational attainment, having a job, having heard about Zika and a good attitude towards childhood vaccination were associated with ZV acceptance in the univariate analyses. In the multivariate analysis, attitude towards childhood vaccination was the strongest predictor for ZV vaccination. We found the geometric mean and median of WTP was US$ 13.1 (95% CI: 11.37-15.09) and US$ 7.0 (95% CI: 4.47-10.98), respectively. In the final model, having heard about Zika, having a job, and higher income were associated with a higher WTP.
CONCLUSION: Although the acceptance rate of the ZV is relatively high in Indonesia, less than 40% of respondents are willing to pay, underscoring the need for a low-cost, high-quality vaccine and public sector subsidies for Zika vaccinations in the country.

Matched MeSH terms: Zika Virus Infection/prevention & control*
Fulltext Willingness to Participate and Associated Factors in a Zika Vaccine Trial in Indonesia: A Cross-Sectional Study

Harapan H, Mudatsir M, Yufika A, Nawawi Y, Wahyuniati N, Anwar S, et al.

Viruses, 2018 11 18;10(11).
PMID: 30453663 DOI: 10.3390/v10110648

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.

Matched MeSH terms: Zika Virus Infection/prevention & control*
Fulltext Diagnosis and management of Guillain-Barré syndrome in ten steps

Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al.

Nat Rev Neurol, 2019 Nov;15(11):671-683.
PMID: 31541214 DOI: 10.1038/s41582-019-0250-9

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

Matched MeSH terms: Zika Virus Infection/diagnosis; Zika Virus Infection/epidemiology; Zika Virus Infection/therapy
Fulltext Field demonstration of the usefulness of a model of 3D printed mosquito light trap made in Sabah

Shigeharu Sato, Tomonori Hoshi, Bumpei Tojo, Samson Yodot, Joni Jain

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):80-80.
MyJurnal

Introduction: Collecting mosquitoes is essential for research in mosquito-borne diseases, but the light traps used for that purpose are expensive and often difficult to obtain around research fields. We designed a new 3D-printable mosquito light trap that can be made inexpensively anywhere where electricity is available (Hoshi et al, Scientific Reports, in press). In this study, we produced that trap in Sabah and demonstrated its usefulness in the field. Meth-ods: With a 3D printer, the main parts of the trap - body, lid, lamp stand and collection box - were printed in Kota Kinabalu using black polylactic acid (PLA) filaments purchased online. All other parts such as the computer fan and batteries were commercially available at local shops in Sabah. The parts were assembled into the complete units at Universiti Malaysia Sabah’s Rural Medical Education Centre (RMEC) in Sikuati, Kudat. Demonstration was performed at two sites in the Kudat district: RMEC campus and the premises of a local farm in Kampung Paradason. Results: The 3D traps collected 6 and 7 different species of mosquitoes at RMEC and Paradason sites, respectively. The numbers of mosquito species collected by the commercially-available CDC model-512 traps in parallel experiments were 2 (RMEC) and 10 (Paradason). The species collected by the 3D traps included Aedes albopictus (vector transmitting Dengue virus), Anopheles barbumbrosus (malaria), Culex quinquefasciatus (Wuchereria bancrofti, avian malaria, and arboviruses including Japanese encephalitis and Zika viruses) and Mansonia indiana (Brugia malayi). Conclu-sion: The 3D light trap which was produced in Sabah demonstrated its usefulness in the field tests performed in the Kudat district. This model can be used as an alternative to the rather expensive commercial light traps to collect the vector insects transmitting mosquito-borne diseases such as malaria, dengue, Japanese encephalitis, Zika fever and filariasis.

Matched MeSH terms: Zika Virus Infection
Fulltext Phylogenetic surveillance of travel-related Zika virus infections through whole-genome sequencing methods

Kamelian K, Montoya V, Olmstead A, Dong W, Harrigan R, Morshed M, et al.

Sci Rep, 2019 Nov 11;9(1):16433.
PMID: 31712570 DOI: 10.1038/s41598-019-52613-8

In 2018, the World Health Organization identified the Zika virus (ZIKV) as a pathogen that should be prioritized for public health research due to its epidemic potential. In this study, whole-genome sequencing (WGS) of travel-acquired ZIKV infections was used to examine the limitations of phylogenetic analysis. WGS and phylogenetic analysis were performed to investigate geographic clustering of samples from five Canadians with travel-acquired ZIKV infections and to assess the limitations of phylogenetic analysis of ZIKV sequences using a phylogenetic cluster approach. Genomic variability of ZIKV samples was assessed and for context, compared with hepatitis C virus (HCV) samples. Phylogenetic analysis confirmed the suspected region of ZIKV infection for one of five samples and one sample failed to cluster with sequences from its suspected country of infection. Travel-acquired ZIKV samples depicted low genomic variability relative to HCV samples. A floating patristic distance threshold classified all pre-2000 ZIKV sequences into separate clusters, while only Cambodian, Peruvian, Malaysian, and South Korean sequences were similarly classifiable. While phylogenetic analysis of ZIKV data can identify the broad geographical region of ZIKV infection, ZIKV's low genomic variability is likely to limit precise interpretations of phylogenetic analysis of the origins of travel-related cases.

Matched MeSH terms: Zika Virus Infection/epidemiology*; Zika Virus Infection/transmission*; Zika Virus Infection/virology*
Fulltext Zika outbreak emergency preparedness and response of Malaysian private healthcare professionals: are they ready?

Rajiah K, Maharajan MK, Yin PY, Yee YW, Lin WW, Kean CH

Microorganisms, 2019;7.
DOI: 10.3390/microorganisms7030087

Zika virus has been declared as a public health emergency of international concern. The Center for Disease Control and Prevention has issued guidelines reminding healthcare workers about the importance of taking steps to prevent the spread of Zika virus, how to test and isolate patients suspected of carrying the Zika virus, and how to protect themselves from infection. Therefore, it is of utmost importance for healthcare professionals to be fully aware of Zika virus preparedness, and response measures should an outbreak occur in Malaysia in order to quickly and efficiently contain the outbreak, ensure the safety of individual or healthcare personnel safety, as well as to prevent further spreading of the disease. This research aims to show how prepared Malaysian healthcare professionals are against Zika virus and how well can they respond during an outbreak. In total, 504 healthcare professionals (128 general practitioners, 215 community pharmacists, 161 nurses) from private health clinics were the target population of the four states of Malaysia where Zika cases suspected. The sample size of each category was calculated by using a formula for estimating the population proportion. An additional 10% of the calculated sample size was added to compensate the non-response rate. The Center For Disease Control and Prevention and World Health Organisation provided a checklist to assess how prepared healthcare professionals are for an Zika outbreak. This checklist was modified to a questionnaire in order to assess health care professionals' preparedness and response to the Zika outbreak. Community pharmacists are still lacking in their preparedness and perceived response to the Zika outbreak compared to the general practitioners in the private sector. Hence community pharmacists should attend training given by the Ministry of Health Malaysia as a continuing education, which may help them to respond during a Zika outbreak.

Matched MeSH terms: Zika Virus Infection
Fulltext A systematic bioinformatics approach for large-scale identification and characterization of host-pathogen shared sequences

James SA, Ong HS, Hari R, Khan AM

BMC Genomics, 2021 Sep 28;22(Suppl 3):700.
PMID: 34583643 DOI: 10.1186/s12864-021-07657-4

BACKGROUND: Biology has entered the era of big data with the advent of high-throughput omics technologies. Biological databases provide public access to petabytes of data and information facilitating knowledge discovery. Over the years, sequence data of pathogens has seen a large increase in the number of records, given the relatively small genome size and their important role as infectious and symbiotic agents. Humans are host to numerous pathogenic diseases, such as that by viruses, many of which are responsible for high mortality and morbidity. The interaction between pathogens and humans over the evolutionary history has resulted in sharing of sequences, with important biological and evolutionary implications.
RESULTS: This study describes a large-scale, systematic bioinformatics approach for identification and characterization of shared sequences between the host and pathogen. An application of the approach is demonstrated through identification and characterization of the Flaviviridae-human share-ome. A total of 2430 nonamers represented the Flaviviridae-human share-ome with 100% identity. Although the share-ome represented a small fraction of the repertoire of Flaviviridae (~ 0.12%) and human (~ 0.013%) non-redundant nonamers, the 2430 shared nonamers mapped to 16,946 Flaviviridae and 7506 human non-redundant protein sequences. The shared nonamer sequences mapped to 125 species of Flaviviridae, including several with unclassified genus. The majority (~ 68%) of the shared sequences mapped to Hepacivirus C species; West Nile, dengue and Zika viruses of the Flavivirus genus accounted for ~ 11%, ~ 7%, and ~ 3%, respectively, of the Flaviviridae protein sequences (16,946) mapped by the share-ome. Further characterization of the share-ome provided important structural-functional insights to Flaviviridae-human interactions.
CONCLUSION: Mapping of the host-pathogen share-ome has important implications for the design of vaccines and drugs, diagnostics, disease surveillance and the discovery of unknown, potential host-pathogen interactions. The generic workflow presented herein is potentially applicable to a variety of pathogens, such as of viral, bacterial or parasitic origin.

Matched MeSH terms: Zika Virus Infection*
Immunofluorescence-based biosensor for the determination of dengue virus NS1 in clinical samples

Darwish NT, Sekaran SD, Alias Y, Khor SM

J Pharm Biomed Anal, 2018 Feb 05;149:591-602.
PMID: 29197806 DOI: 10.1016/j.jpba.2017.11.064

The sharp increase in incidence of dengue infection has necessitated the development of methods for the rapid diagnosis of this deadly disease. Here we report the design and development of a reliable, sensitive, and specific optical immunosensor for the detection of the dengue nonstructural protein 1 (NS1) biomarker in clinical samples obtained during early stages of infection. The present optical NS1 immunosensor comprises a biosensing surface consisting of specific monoclonal NS1 antibody for immunofluorescence-based NS1 antigen determination using fluorescein isothiocyanate (FITC) conjugated to IgG antibody. The linear range of the optical immunosensor was from 15-500ngmL-1, with coefficient of determination (R2) of 0.92, high reproducibility (the relative standard deviation obtained was 2%), good stability for 21days at 4°C, and low detection limit (LOD) at 15ngmL-1. Furthermore, the optical immunosensor was capable of detecting NS1 analytes in plasma specimens from patients infected with the dengue virus, with low cross-reaction with plasma specimens containing the Japanese encephalitis virus (JEV) and Zika virus. No studies have been performed on the reproducibility and cross-reactivity regarding NS1 specificity, which is thus a limitation for optical NS1 immunosensors. In contrast, the present study addressed these limitations carefully where these two important experiments were conducted to showcase the robustness of our newly developed optical-based fluorescence immunosensor, which can be practically used for direct NS1 determination in any untreated clinical sample.

Matched MeSH terms: Zika Virus Infection/blood; Zika Virus Infection/virology
Fulltext Fetal Brain Infection Is Not a Unique Characteristic of Brazilian Zika Viruses

Setoh YX, Peng NY, Nakayama E, Amarilla AA, Prow NA, Suhrbier A, et al.

Viruses, 2018 10 03;10(10).
PMID: 30282919 DOI: 10.3390/v10100541

The recent emergence of Zika virus (ZIKV) in Brazil was associated with an increased number of fetal brain infections that resulted in a spectrum of congenital neurological complications known as congenital Zika syndrome (CZS). Herein, we generated de novo from sequence data an early Asian lineage ZIKV isolate (ZIKV-MY; Malaysia, 1966) not associated with microcephaly and compared the in vitro replication kinetics and fetal brain infection in interferon α/β receptor 1 knockout (IFNAR1-/-) dams of this isolate and of a Brazilian isolate (ZIKV-Natal; Natal, 2015) unequivocally associated with microcephaly. The replication efficiencies of ZIKV-MY and ZIKV-Natal in A549 and Vero cells were similar, while ZIKV-MY replicated more efficiently in wild-type (WT) and IFNAR-/- mouse embryonic fibroblasts. Viremias in IFNAR1-/- dams were similar after infection with ZIKV-MY or ZIKV-Natal, and importantly, infection of fetal brains was also not significantly different. Thus, fetal brain infection does not appear to be a unique feature of Brazilian ZIKV isolates.

Matched MeSH terms: Zika Virus Infection/pathology*; Zika Virus Infection/virology*
Fulltext Co-breeding Association of Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus) (Diptera: Culicidae) in Relation to Location and Container Size

Hashim NA, Ahmad AH, Talib A, Athaillah F, Krishnan KT

Trop Life Sci Res, 2018 Mar;29(1):213-227.
PMID: 29644025 MyJurnal DOI: 10.21315/tlsr2018.29.1.14

The occurrence of major outbreaks of dengue, and other vector borne diseases such as chikungunya and zika in tropical and subtropical regions has rendered control of the diseases a top-priority for many affected countries including Malaysia. Control of the mosquito vectors Aedes aegypti and Aedes albopictus through the reduction of breeding sites and the application of insecticides to kill immature forms and adults are the main control efforts to combat these diseases. The present study describes the association between Ae. albopictus and Ae. aegypti in shared breeding sites. This study is important given that any measure taken against one species may affect the other. A yearlong larval survey was conducted in four dengue endemic areas of Penang Island. Sorenson's coefficient index indicated that no association between number of the immatures of the two species regardless of container size and study location. Therefore, the mean number Ae. albopictus immature was not decreased in the presence of Ae. aegypti in shared breeding container. However Ae. aegypti appeared to prefer breeding in habitats not occupied by Ae. albopictus, the two species sharing breeding sites only where available containers were limited. In control efforts, eliminating the preferred breeding containers for one species might not affect or reduce the population of the other species.

Matched MeSH terms: Zika Virus Infection
Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes

Uncini A, Shahrizaila N, Kuwabara S

J Neurol Neurosurg Psychiatry, 2017 03;88(3):266-271.
PMID: 27799296 DOI: 10.1136/jnnp-2016-314310

In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.

Matched MeSH terms: Zika Virus Infection/epidemiology
Fulltext Entomological Surveillance Associated with Human Zika Cases in Miri Sarawak, Malaysia

Ali R, Azmi RA, Wasi Ahmad N, Abd Hadi A, Muhamed KA, Rasli R, et al.

Am J Trop Med Hyg, 2020 May;102(5):964-970.
PMID: 32228777 DOI: 10.4269/ajtmh.19-0339

Two confirmed human cases of Zika virus (ZIKV) were reported in the district of Miri, Sarawak, in 2016. Following that, a mosquito-based ZIKV surveillance study was conducted within 200-m radius from the case houses. Mosquito surveillance was conducted using five different methods, that is, biogents sentinel mosquito (BG) sentinel trap, modified sticky ovitrap, resting catch, larval surveillance, and conventional ovitrap. A total of 527 and 390 mosquito samples were obtained from the case houses in two localities, namely, Kampung Lopeng and Taman Shang Ri La, Miri, Sarawak, respectively. All mosquitoes collected were identified, which consisted of 11 species. Aedes albopictus, both the adult and larval stages, was the dominant species. Resting catch method obtained the highest number of adult mosquitoes (67%), whereas ovitrap showed the highest catch for larval mosquitoes (84%). Zika virus was detected in both adults and larvae of Ae. albopictus together with adults of Culex gelidus, and Culex quinquefasciatus using the real-time reverse transcriptase polymerase chain reaction (PCR) technique. It was noteworthy that Ae. albopictus positive with ZIKV were caught and obtained from four types of collection method. By contrast, Cx. gelidus and Culex quinquefasciatus adults collected from sticky ovitraps were also found positive with ZIKV. This study reveals vital information regarding the potential vectors of ZIKV and the possibility of transovarian transmission of the virus in Malaysia. These findings will be essentials for vector control program managers to devise preparedness and contingency plans of prevention and control of the arboviral disease.

Matched MeSH terms: Zika Virus Infection/etiology; Zika Virus Infection/epidemiology*; Zika Virus Infection/transmission
Complete Genome Sequences of Three Historically Important, Spatiotemporally Distinct, and Genetically Divergent Strains of Zika Virus: MR-766, P6-740, and PRVABC-59

Yun SI, Song BH, Frank JC, Julander JG, Polejaeva IA, Davies CJ, et al.

Genome Announc, 2016;4(4).
PMID: 27540058 DOI: 10.1128/genomeA.00800-16

Here, we report the 10,807-nucleotide-long consensus RNA genome sequences of three spatiotemporally distinct and genetically divergent Zika virus strains, with the functionality of their genomic sequences substantiated by reverse genetics: MR-766 (African lineage, Uganda, 1947), P6-740 (Asian lineage, Malaysia, 1966), and PRVABC-59 (Asian lineage-derived American strain, Puerto Rico, 2015).

Matched MeSH terms: Zika Virus Infection
Fulltext Functional Genomics and Immunologic Tools: The Impact of Viral and Host Genetic Variations on the Outcome of Zika Virus Infection

Yun SI, Song BH, Frank JC, Julander JG, Olsen AL, Polejaeva IA, et al.

Viruses, 2018 08 11;10(8).
PMID: 30103523 DOI: 10.3390/v10080422

Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously undescribed gene products identified in the case of all three molecularly cloned ZIKVs. (ii) We found that ZIKV has a broad cell tropism in vitro, being capable of establishing productive infection in 16 of 17 animal cell lines from 12 different species, although its growth kinetics varied depending on both the specific virus strain and host cell line. More importantly, we identified one ZIKV-non-susceptible bovine cell line that has a block in viral entry but fully supports the subsequent post-entry steps. (iii) We showed that in mice, the three molecularly cloned ZIKVs differ in their neuropathogenicity, depending on the particular combination of viral and host genetic backgrounds, as well as in the presence or absence of type I/II interferon signaling. Overall, our findings demonstrate the impact of viral and host genetic variations on the replication kinetics and neuropathogenicity of ZIKV and provide multiple avenues for developing and testing medical countermeasures against ZIKV.

Matched MeSH terms: Zika Virus Infection/genetics*; Zika Virus Infection/virology
Zika Virus Infection: Current Concerns and Perspectives

Maharajan MK, Ranjan A, Chu JF, Foo WL, Chai ZX, Lau EY, et al.

Clin Rev Allergy Immunol, 2016 Dec;51(3):383-394.
PMID: 27236440

The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer-reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness.

Matched MeSH terms: Zika Virus Infection/diagnosis*; Zika Virus Infection/drug therapy; Zika Virus Infection/transmission; Zika Virus Infection/virology*
Fulltext Pyrethroid resistance in the dengue vector Aedes aegypti in Southeast Asia: present situation and prospects for management

Amelia-Yap ZH, Chen CD, Sofian-Azirun M, Low VL

Parasit Vectors, 2018 Jun 04;11(1):332.
PMID: 29866193 DOI: 10.1186/s13071-018-2899-0

Human arboviral diseases transmitted by Aedes aegypti such as dengue, Zika, chikungunya and yellow fever remain global public health threats to date. Of these diseases, dengue fever is particularly prevalent in Southeast Asia. Relentless vector control efforts are performed to curtail disease transmissions through which pyrethroid insecticides are broadly used as the first line of defense to control Ae. aegypti, especially in the course of disease outbreaks. Here, we compile the largest contemporary database for susceptibility profiles and underlying mechanisms involved in Ae. aegypti resistant to pyrethroids in Southeast Asia. The extensive use of pyrethroids inevitably elicit different levels of resistance to numerous populations despite the presence of geographical isolation. The most common mechanisms of pyrethroid resistance that have been identified in Ae. aegypti includes mutations in the voltage sensitive sodium channel gene (Vssc gene) and metabolic-mediated insecticide resistance. Aedes aegypti develops resistance to pyrethroids by acquisition of one or several amino acid substitution(s) in this Vssc gene. Enzymes involved in metabolic-mediated detoxification (i.e. monooxygenases, glutathione-S-transferases and esterases) have been reported to be related to pyrethroid resistance but many specific contributory enzymes are not completely studied. An inadequate amount of data from some countries indicates an urgent need for further study to fill the knowledge gaps. Perspectives and future research needs are also discussed.

Matched MeSH terms: Zika Virus Infection/transmission*
Fulltext Host immune response against DENV and ZIKV infections

Sekaran SD, Ismail AA, Thergarajan G, Chandramathi S, Rahman SKH, Mani RR, et al.

Front Cell Infect Microbiol, 2022;12:975222.
PMID: 36159640 DOI: 10.3389/fcimb.2022.975222

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.

Matched MeSH terms: Zika Virus Infection*
Fulltext Zika - A Pandemic in Progress?

Mohamad Idris F

Malays J Med Sci, 2016 Mar;23(2):70-2.
PMID: 27547117

The emerging threat of Zika virus outbreak with associated neurological abnormalities needs to be assessed in perspective in terms of its ability to cause a pandemic. This article attempts to throw some light on the issue.

Matched MeSH terms: Zika Virus Infection

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