scholarly journals Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1878
Author(s):  
Karla Ausderau ◽  
Sabrina Kabakov ◽  
Elaina Razo ◽  
Ann M. Mitzey ◽  
Kathryn M. Bach ◽  
...  
Keyword(s):  
Zika Virus ◽  
Developmental Outcomes ◽  
Denv Infection ◽  
Visual Orientation ◽  
State Control ◽  
Zikv Infection ◽  
Macaque Model ◽  
Multiple Factors ◽  
Exposed Infant

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

scholarly journals Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

2018 ◽  
Author(s):  
Felix G. Delgado ◽  
Karina I. Torres ◽  
Jaime E. Castellanos ◽  
Consuelo Romero-Sánchez ◽  
Etienne Simon-Lorière ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses ◽  
B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where 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 infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using 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 non-structural 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.

scholarly journals Zika virus: a new pandemic threat

2016 ◽  
Vol 10 (03) ◽  
pp. 201-207 ◽  
Author(s):  
Ahmed Ali Al-Qahtani ◽  
Nyla Nazir ◽  
Mashael R. Al-Anazi ◽  
Salvatore Rubino ◽  
Mohammed N. Al-Ahdal
Keyword(s):  
Zika Virus ◽  
Blood Donation ◽  
French Polynesia ◽  
Western Hemisphere ◽  
Zikv Infection ◽  
Rapid Spread ◽  
Screening And Identification ◽  
Pandemic Threat ◽  
Contaminated Blood

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important.

scholarly journals Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Himanshu Garg ◽  
Rose Yeh ◽  
Douglas M. Watts ◽  
Tugba Mehmetoglu-Gurbuz ◽  
Robert Resendes ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Zika Virus ◽  
Human Subjects ◽  
Denv Infection ◽  
Serum Samples ◽  
Endemic Region ◽  
West Nile ◽  
Zikv Infection ◽  
Antigenic Relatedness

Abstract Background Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. Results Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. Conclusions Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.

scholarly journals Late Neurological Consequences of Zika Virus Infection: Risk Factors and Pharmaceutical Approaches

2019 ◽  
Vol 12 (2) ◽  
pp. 60 ◽  
Author(s):  
Isis N. O. Souza ◽  
Fernanda G. Q. Barros-Aragão ◽  
Paula S. Frost ◽  
Claudia P. Figueiredo ◽  
Julia R. Clarke
Keyword(s):  
Zika Virus ◽  
Late Onset ◽  
Neurological Complications ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Clinical Surveillance ◽  
Infection Risk Factors

Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially after the 2015 epidemics in the American continent. The development or severity of these conditions cannot be fully predicted, but it is possible that genetic, epigenetic, and environmental factors may contribute to determine ZIKV infection outcomes. This reinforces the importance that individuals exposed to ZIKV are submitted to long-term clinical surveillance and highlights the urgent need for the development of therapeutic approaches to reduce or eliminate the neurological burden of infection. Here, we review the epidemiology of ZIKV-associated neurological complications and the role of factors that may influence disease outcome. Moreover, we discuss experimental and clinical evidence of drugs that have shown promising results in vitro or in vitro against viral replication and and/or ZIKV-induced neurotoxicity.

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

2017 ◽  
Vol 56 (3) ◽  
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.

scholarly journals Evidence of Zika virus circulation in asymptomatic pregnant women in Northeast, Brazil

2021 ◽  
Vol 15 (6) ◽  
pp. e0009412
Author(s):  
Rebeca Costa Castelo Branco ◽  
Patrícia Brasil ◽  
Josélio Maria Galvão Araújo ◽  
Flávia Oliveira Cardoso ◽  
Zulmira Silva Batista ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Umbilical Cord ◽  
Zika Virus ◽  
Venous Blood ◽  
Rapid Test ◽  
Northeast Brazil ◽  
Zikv Infection ◽  
Long Term Impact ◽  
Maternity Clinics

Background Zika virus (ZIKV) is a flavivirus associated with microcephaly and other fetal anormalities. However, evidence of asymptomatic ZIKV infection in pregnant women is still scarce. This study investigated the prevalence of Zika infection in asymptomatic pregnant women attending two public maternities in Maranhão state, Northeast Brazil. Methods A total of 196 women were recruited at the time of delivery by convenience sampling from two maternity clinics in São Luís, Maranhão, Brazil, between April 2017 and June 2018. Venous blood, umbilical cord blood and placental fragments from maternal and fetal sides were collected from each subject. ZIKV infection was determined by reverse transcription polymerase chain reaction (RT-qPCR) for ZIKV and by serology (IgM and IgG). Nonspecific laboratory profiles (TORCH screen) were obtained from medical records. Results The participants were mostly from São Luís and were of 19–35 years of age. They had 10–15 years of schooling and they were of mixed race, married, and Catholic. ZIKV was identified in three umbilical cord samples and in nine placental fragments. Mothers with positive ZIKV RT-qPCR were in the age group older than 19 years. Of the 196 women tested by ZIKV rapid test, 6 and 117 women were positive for anti-ZIKV IgM and anti-ZIKV IgG antibodies, respectively. Placental Immunohistochemistry study detected ZIKV in all samples positive by RT-PCR. The newborns did not show any morphological and/or psychomotor abnormalities at birth. Conclusions Asymptomatic ZIKV infection is frequent, but it was not associated to morphological and/or psychomotor abnormalities in the newborns up to 6 months post-birth. Although pathological abnormalities were not observed at birth, we cannot rule out the long term impact of apparent asymptomatic congenital ZIKV infection.

scholarly journals Neonatal Zika virus infection causes epileptic seizures, viral persistence and long-term behavioral impairment

2017 ◽  
Author(s):  
Isis N. O. Souza ◽  
Paula S. Frost ◽  
Julia V. França ◽  
Jéssica Nascimento-Viana ◽  
Rômulo L. S. Neris ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neurological Disorders ◽  
Epileptic Seizures ◽  
Immunocompetent Mouse ◽  
Behavioral Impairment ◽  
Zikv Infection ◽  
Chemically Induced ◽  
Tnf Α ◽  
Mice Brain

AbstractA causal relationship between congenital Zika virus (ZIKV) exposure and microcephaly and other neurological disorders have been established, but long-term consequences of infection are still unknown. We evaluated acute and late neuropathological and behavioral consequences of ZIKV infection in a neonatal immunocompetent mouse model. ZIKV showed brain tropism, causing post-natal microcephaly and several behavioral dysfunctions. During the acute phase of infection, mice developed very frequent epileptic seizures, which are consistently reduced by TNF-α neutralization. Although adult animals recover from seizures, they become more susceptible to chemically-induced crises. Intriguingly, the virus remained actively replicating in adult animals, which show persistent necrosis and calcifications in the mice brain. Altogether the results reveal late consequences of neonatal ZIKV exposure and suggest the early inhibition of neuroinflammation as a potential treatment.

scholarly journals Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques

2019 ◽  
Author(s):  
Meghan E. Breitbach ◽  
Christina M. Newman ◽  
Dawn M. Dudley ◽  
Laurel M. Stewart ◽  
Matthew T. Aliota ◽  
...  
Keyword(s):  
Zika Virus ◽  
Primary Infection ◽  
Rhesus Macaques ◽  
Secondary Infection ◽  
Denv Infection ◽  
The Other ◽  
Sample Type ◽  
Zikv Infection ◽  
Secondary Infections ◽  
Cynomolgus Macaques

AbstractZika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.Author summaryPre-existing immunity to one of the four DENV serotypes is known to increase the risk of severe disease upon secondary infection with a different serotype. Due to the antigenic similarities between ZIKV and DENV, it has been proposed that these viruses could interact in a similar fashion. Data from in vitro experiments and murine models suggests that pre-existing immunity to one virus could either enhance or protect against infection with the other. These somewhat contradictory findings highlight the need for immune competent animal models for understanding the role of cross-reactive antibodies in flavivirus pathogenesis. We examined secondary ZIKV or DENV infections in rhesus and cynomolgus macaques that had previously been infected with the other virus. We assessed the outcomes of secondary ZIKV or DENV infections by quantifying vRNA loads, clinical and laboratory parameters, body temperature, and weight for each cohort of animals and compared them with control animals. These comparisons demonstrated that within a year of primary infection, secondary infections with either ZIKV or DENV were similar to primary infections and were not associated with enhancement or reduction in severity of disease based on the outcomes that we assessed.

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

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.

scholarly journals Persistence of Anti-Zika Virus Immunoglobulin M Antibodies in Children with Microcephaly up to Four Years after Primary Infection

2019 ◽  
Author(s):  
Gubio S. Campos ◽  
Rejane H. Carvalho ◽  
Maria da Glória Teixeira ◽  
Giovanna F. Britto e Silva ◽  
Carolina A. Rolo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Primary Infection ◽  
Immune Reaction ◽  
Acute Infection ◽  
Immunoglobulin M ◽  
Zikv Infection ◽  
Igm Antibodies ◽  
Igm Antibody ◽  
Antibody Persistence

AbstractZika virus (ZIKV) is a member of the flaviviridae family of virus, considered to cause acute self-limited infection in adults, though it may lead to severe complications. It is believed that ZIKV infection elicit a classical viral immune reaction, with primary IgM antibody response and secondary IgG immunity. Persistence of IgM antibodies has been identified for other viruses belonging to the same family as ZIKV. We investigated, therefore, the presence of anti-ZIKV IgM antibodies in children with microcephaly born between January 2015 and November 2018, and their parents. We have detected persistence of IgM in 22% of children with microcephaly up to four years after primary infection. Long term IgM persistence have implications for the diagnosis of acute infection. More investigation is needed in order to correctly construe the significance of anti-ZIKV IgM persistence in the population in general, and in children with microcephaly in particular. The dynamics of IgM antibody responses against ZIKV must be known and understood to avoid misinterpretation of diagnosis for acute infection, re-infection and antibody persistence.

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