Zika Virus: Unanswered Questions

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 21379

Special Issue Editor


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Guest Editor
School of Medicine, Tulane University, New Orleans, LA, USA
Interests: interferon; virus; zika; dengue; SARS-CoV-2

Special Issue Information

Dear Colleagues,

The mosquito-borne virus Zika virus has come and gone from the popular press, but many questions related to Zika pathogenicity, long-term consequences, and countermeasures remain unanswered. For instance, is Zika virus transmission ongoing, and, if so, where? How has Zika virus immunity affected anti-dengue immune response and pathogenicity? Are additional cases of Zika-associated microcephaly being reported, and are we keeping track of longer-term consequences of Zika? What progress have we made toward understanding the mechanism of Zika-associated microcephaly? What countermeasures do we have in hand for Zika? What is the status of current Zika surveillance methods, and will this help us to detect other emerging pathogens more effectively? We invite you to keep in mind that, in these post-COVID times, ongoing study of other viral pathogens is crucial.

Dr. Dahlene Fusco
Guest Editor

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Keywords

  • zika virus
  • flavivirus
  • countermeasure

Published Papers (8 papers)

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Research

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10 pages, 977 KiB  
Article
Seroprevalence of Zika Virus in Amphawa District, Thailand, after the 2016 Pandemic
by Salin Sirinam, Supawat Chatchen, Watcharee Arunsodsai, Suriya Guharat and Kriengsak Limkittikul
Viruses 2022, 14(3), 476; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030476 - 25 Feb 2022
Cited by 4 | Viewed by 1777
Abstract
In 2016, Zika virus (ZIKV) infection was declared a public health emergency of international concern because of the neurological consequences in babies born to infected people. Because of the mild and nonspecific symptoms, serological tests are essential in epidemiological studies. However, cross-reactive antibodies [...] Read more.
In 2016, Zika virus (ZIKV) infection was declared a public health emergency of international concern because of the neurological consequences in babies born to infected people. Because of the mild and nonspecific symptoms, serological tests are essential in epidemiological studies. However, cross-reactive antibodies between other Flaviviridae members may complicate the interpretation of results of these tests. This study investigated the seroprevalence of ZIKV infection in Samut Songkhram in central Thailand which was affected by the Zika outbreak of 2016. Three hundred and fifty volunteers aged 5–50 years in Amphawa District, Samut Songkhram, were enrolled between April 2017 and April 2018. ZIKV nonstructural protein 1 (NS1) immunoglobulin G enzyme-linked immunosorbent assay (ELISA) was used to screen serum samples collected on the first day of enrollment and after 6 and 12 months. The seroprevalence and seroconversion of ZIKV were assessed. Cases of ZIKV seroconversion were verified as evidence of ZIKV infection by NS1 blockade-of-binding ELISA and plaque reduction neutralization test (PRNT50). ZIKV seroprevalence in Amphawa was 15.1–17.8% with no significant change over the year. The total seroconversion rate throughout the year was 7/100 person-years. The ratio of asymptomatic to symptomatic infections was 4.5:1. The cases in our study confirmed the occurrence of occult ZIKV infections in the community. These undetected infections might promote the spread of ZIKV in vulnerable groups of the community. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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13 pages, 696 KiB  
Article
Zika Virus Immunoglobulin G Seroprevalence among Young Adults Living with HIV or without HIV in Thailand from 1997 to 2017
by Sirinath Choyrum, Nantawan Wangsaeng, Anouar Nechba, Nicolas Salvadori, Rumpaiphorn Saisom, Jullapong Achalapong, Chaiwat Putiyanun, Prapan Sabsanong, Suraphan Sangsawang, Orada Patamasingh Na Ayudhaya, Gonzague Jourdain, Nicole Ngo-Giang-Huong and Woottichai Khamduang
Viruses 2022, 14(2), 368; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020368 - 10 Feb 2022
Viewed by 1460
Abstract
Zika virus (ZIKV) epidemiological data in Thailand are limited. We assessed ZIKV IgG seroprevalence among young adults during 1997–2017 and determined factors associated with ZIKV IgG seropositivity. This retrospective laboratory study included randomly selected subjects aged 18–25 years participating in large clinical studies [...] Read more.
Zika virus (ZIKV) epidemiological data in Thailand are limited. We assessed ZIKV IgG seroprevalence among young adults during 1997–2017 and determined factors associated with ZIKV IgG seropositivity. This retrospective laboratory study included randomly selected subjects aged 18–25 years participating in large clinical studies conducted in Thailand during 1997–2017. Stored plasma samples were analyzed for ZIKV IgG using an ELISA test (Anti-Zika Virus IgG, EUROIMMUN, Lübeck, Germany). Sociodemographic, clinical and laboratory data were used in univariable and multivariable analyses to identify factors associated with ZIKV IgG positivity. Of the 1648 subjects included, 1259 were pregnant women, 844 were living with HIV and 111 were living with HBV. ZIKV IgG seroprevalence was similar among the HIV-infected and -uninfected pregnant women (22.8% vs. 25.8%, p-value = 0.335) and was overall stable among the pregnant women, with a 25.2% prevalence. Factors independently associated with ZIKV IgG positivity included an age of 23–25 years as compared to 18–20 years, an HIV RNA load below 3.88 log10 copies/mL and birth in regions outside northern Thailand. Our study shows that a large proportion of the population in Thailand probably remains susceptible to ZIKV infection, which could be the ground for future outbreaks. Continued surveillance of ZIKV spread in Thailand is needed to inform public health policies. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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10 pages, 1422 KiB  
Article
Incidence of Zika Virus Infection from a Dengue Epidemiological Study of Children in Ratchaburi Province, Thailand
by Pimolpachr Sriburin, Pichamon Sittikul, Nathamon Kosoltanapiwat, Salin Sirinam, Watcharee Arunsodsai, Chukiat Sirivichayakul, Kriengsak Limkittikul and Supawat Chatchen
Viruses 2021, 13(9), 1802; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091802 - 10 Sep 2021
Cited by 6 | Viewed by 1823
Abstract
Zika virus (ZIKV) is the mosquito-transmitted virus that the WHO declared a Public Health Emergency of International Concern in 2016 due to the consequence of microcephaly from infected pregnancies. The incidence of Zika infection has been unclear in many countries because most infected [...] Read more.
Zika virus (ZIKV) is the mosquito-transmitted virus that the WHO declared a Public Health Emergency of International Concern in 2016 due to the consequence of microcephaly from infected pregnancies. The incidence of Zika infection has been unclear in many countries because most infected people have nonspecific febrile illnesses. This study’s aim is to investigate the incidence of symptomatic Zika virus infections from the archived samples of a dengue cohort study of children in central Thailand from 2006 to 2009. We performed Zika NS1 immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) screening to identify symptomatic Zika infections in paired acute/convalescent serum samples. Symptomatic Zika infections were confirmed by reverse transcription polymerase chain reactions (RT-PCR) of acute serum samples. The comparison of the Zika NS1 IgG ELISA results between acute and convalescent samples showed 290/955 (30.4%) seropositive cases. Zika RT-PCR results were positive in 28 febrile cases (15 females, 13 males). Zika RT-PCR showed that symptomatic Zika infection occurred in children aged 4–11 years in Ratchaburi province, Thailand (2007–2009, first case in April 2007), and the symptomatic Zika:dengue infection ratio was 28 Zika:394 dengue (1:14). Phylogenetic analysis showed that all Zika viruses were of Asian lineage. Zika NS1 IgG ELISA identified Zika-infected patients and showed a low Zika:dengue ratio. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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17 pages, 3289 KiB  
Article
Zika Virus Non-Structural Protein 1 Antigen-Capture Immunoassay
by Brandon J. Beddingfield, Jessica N. Hartnett, Russell B. Wilson, Peter C. Kulakosky, Kristian G. Andersen, Refugio Robles-Sikisaka, Nathan D. Grubaugh, Argelia Aybar, Maria-Zunilla Nunez, Cesar D. Fermin and Robert F. Garry
Viruses 2021, 13(9), 1771; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091771 - 05 Sep 2021
Cited by 5 | Viewed by 3272
Abstract
Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the [...] Read more.
Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modify putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 and 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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8 pages, 440 KiB  
Article
Lack of Association between Adverse Pregnancy Outcomes and Zika Antibodies among Pregnant Women in Thailand between 1997 and 2015
by Nicole Ngo-Giang-Huong, Charline Leroi, Dahlene Fusco, Tim R. Cressey, Nantawan Wangsaeng, Nicolas Salvadori, Natedao Kongyai, Wasna Sirirungsi, Marc Lallemant, Prasert Auewarakul, Woottichai Khamduang and Gonzague Jourdain
Viruses 2021, 13(8), 1423; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081423 - 22 Jul 2021
Cited by 2 | Viewed by 2428
Abstract
Data about Zika virus infection and adverse pregnancy outcomes in Southeast Asia are scarce. We conducted an unmatched case-control study of Zika virus (ZIKV) serology in pregnant women enrolled in human immunodeficiency virus (HIV) or hepatitis B virus (HBV) perinatal prevention trials between [...] Read more.
Data about Zika virus infection and adverse pregnancy outcomes in Southeast Asia are scarce. We conducted an unmatched case-control study of Zika virus (ZIKV) serology in pregnant women enrolled in human immunodeficiency virus (HIV) or hepatitis B virus (HBV) perinatal prevention trials between 1997 and 2015 in Thailand. Case and control groups included women with and without adverse pregnancy outcomes. Plasma samples collected during the last trimester of pregnancy were tested for ZIKV IgG/IgM and Dengue IgG/IgM (Euroimmun, AG, Germany). Case newborn plasma samples were tested for ZIKV IgM and ZIKV RNA (Viasure, Spain). The case group included women with stillbirth (n = 22) or whose infants had microcephaly (n = 4), a head circumference below the first percentile (n = 14), neurological disorders (n = 36), or had died within 10 days after birth (n = 11). No women in the case group were positive for ZIKV IgM, and none of their live-born neonates were positive for ZIKV IgM or ZIKV RNA. The overall ZIKV IgG prevalence was 29%, 24% in the case and 34% in the control groups (Fisher’s exact test; p = 0.13), while the dengue IgG seroprevalence was 90%. Neither neonatal ZIKV infections nor ZIKV-related adverse pregnancy outcomes were observed in these women with HIV and/or HBV during the 18-year study period. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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Review

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44 pages, 5972 KiB  
Review
Is the ZIKV Congenital Syndrome and Microcephaly Due to Syndemism with Latent Virus Coinfection?
by Solène Grayo
Viruses 2021, 13(4), 669; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040669 - 13 Apr 2021
Cited by 4 | Viewed by 3493
Abstract
The emergence of the Zika virus (ZIKV) mirrors its evolutionary nature and, thus, its ability to grow in diversity or complexity (i.e., related to genome, host response, environment changes, tropism, and pathogenicity), leading to it recently joining the circle of closed congenital pathogens. [...] Read more.
The emergence of the Zika virus (ZIKV) mirrors its evolutionary nature and, thus, its ability to grow in diversity or complexity (i.e., related to genome, host response, environment changes, tropism, and pathogenicity), leading to it recently joining the circle of closed congenital pathogens. The causal relation of ZIKV to microcephaly is still a much-debated issue. The identification of outbreak foci being in certain endemic urban areas characterized by a high-density population emphasizes that mixed infections might spearhead the recent appearance of a wide range of diseases that were initially attributed to ZIKV. Globally, such coinfections may have both positive and negative effects on viral replication, tropism, host response, and the viral genome. In other words, the possibility of coinfection may necessitate revisiting what is considered to be known regarding the pathogenesis and epidemiology of ZIKV diseases. ZIKV viral coinfections are already being reported with other arboviruses (e.g., chikungunya virus (CHIKV) and dengue virus (DENV)) as well as congenital pathogens (e.g., human immunodeficiency virus (HIV) and cytomegalovirus (HCMV)). However, descriptions of human latent viruses and their impacts on ZIKV disease outcomes in hosts are currently lacking. This review proposes to select some interesting human latent viruses (i.e., herpes simplex virus 2 (HSV-2), Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), human parvovirus B19 (B19V), and human papillomavirus (HPV)), whose virological features and co-exposition with ZIKV may provide evidence of the syndemism process, shedding some light on the emergence of the ZIKV-induced global congenital syndrome in South America. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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14 pages, 518 KiB  
Review
Update on the Transmission of Zika Virus Through Breast Milk and Breastfeeding: A Systematic Review of the Evidence
by Elizabeth Centeno-Tablante, Melisa Medina-Rivera, Julia L. Finkelstein, Heather S. Herman, Pura Rayco-Solon, Maria Nieves Garcia-Casal, Lisa Rogers, Kate Ghezzi-Kopel, Mildred P. Zambrano Leal, Joyce K. Andrade Velasquez, Juan G. Chang Asinc, Juan Pablo Peña-Rosas and Saurabh Mehta
Viruses 2021, 13(1), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010123 - 18 Jan 2021
Cited by 12 | Viewed by 3002
Abstract
We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast [...] Read more.
We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding-related practices. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother–children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications was found to be associated with ZIKV RNA in breast milk. This review updates our previous report by including 12 new articles, in which we found no evidence of ZIKV mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to determine if ZIKV can be transmitted through breastfeeding. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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Other

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12 pages, 1555 KiB  
Systematic Review
Congenital Zika Infection and the Risk of Neurodevelopmental, Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review
by Evangelia Antoniou, Eirini Orovou, Paraskevi Eva Andronikidi, Christos Orovas, Nikolaos Rigas, Ermioni Palaska, Angeliki Sarella, Georgios Iatrakis and Chrysa Voyiatzaki
Viruses 2021, 13(8), 1671; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081671 - 23 Aug 2021
Cited by 5 | Viewed by 2362
Abstract
It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental [...] Read more.
It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment. Full article
(This article belongs to the Special Issue Zika Virus: Unanswered Questions)
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