scholarly journals Zika Virus Infection in Pregnancy: Advanced Diagnostic Approaches in Dengue-Naive and Dengue-Experienced Pregnant Women and Possible Implication for Cross-Reactivity and Cross-Protection

2019 ◽  
Vol 8 (1) ◽  
pp. 56 ◽  
Author(s):  
Maurizio Zavattoni ◽  
Francesca Rovida ◽  
Elena Percivalle ◽  
Irene Cassaniti ◽  
Antonella Sarasini ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Zika Virus ◽  
Cross Reactivity ◽  
Cross Protection ◽  
Effector Memory ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Effector Memory T Cells ◽  
Diagnostic Approaches

Zika virus (ZIKV) infection has been linked to congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil. Given the overlapping presence of Dengue virus (DENV) in the majority of ZIKV epidemic regions, advanced diagnostic approaches need to be evaluated to establish the role of pre-existing DENV immunity in ZIKV infection. From 2015 to 2017, five pregnant women with suspected ZIKV infection were investigated in Pavia, Italy. Among the five pregnant women, three were DENV–ZIKV immunologically cross-reactive, and two were DENV-naïve. Advanced diagnosis included the following: (i) NS1 blockade-of-binding (BOB) ELISA assay for ZIKV specific antibodies and (ii) ELISpot assay for the quantification of effector memory T cells for DENV and ZIKV. These novel assays allowed to distinguish between related flavivirus infections. The three DENV-experienced mothers did not transmit ZIKV to the fetus, while the two DENV-naive mothers transmitted ZIKV to the fetus. Pre-existing immunity in DENV experienced mothers might play a role in cross-protection.

scholarly journals Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 80
Author(s):  
Elizabeth Camacho-Zavala ◽  
Clara Santacruz-Tinoco ◽  
Esteban Muñoz ◽  
Rommel Chacón-Salinas ◽  
Ma Isabel Salazar-Sanchez ◽  
...  
Keyword(s):  
Viral Load ◽  
Inflammatory Response ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Zika Virus ◽  
Epidemiological Surveillance ◽  
Congenital Defects ◽  
Serum Samples ◽  
Zikv Infection ◽  
Anti Inflammatory

Background: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. Objective: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. Materials and Methods: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. Results: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. Conclusion: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.

scholarly journals Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela

2021 ◽  
Vol 15 (4) ◽  
pp. e0009336
Author(s):  
Ivonne Morales ◽  
Kerstin D. Rosenberger ◽  
Tereza Magalhaes ◽  
Clarice N. L. Morais ◽  
Cynthia Braga ◽  
...  
Keyword(s):  
Zika Virus ◽  
Test Performance ◽  
Diagnostic Performance ◽  
Cross Reactivity ◽  
Rt Pcr ◽  
Zikv Infection ◽  
Serological Tests ◽  
Sequential Samples

Background Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela. Methodology/Principal findings Acute (day of illness 1–5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study of symptomatic patients recruited between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/48), while IgM and IgG exhibited sensitivities of 30.3% (10/35) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%. Conclusions/Significance Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

scholarly journals Challenges of Zika Virus Testing in Pregnancy in the Setting of Local Mosquito-Borne Transmission

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S302-S302
Author(s):  
Jaclyn Kwal ◽  
Michelle Bartlett ◽  
Anise Crane ◽  
Samantha Greissman ◽  
Naiomi Gunaratne ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Zika Virus ◽  
False Positive ◽  
Clinical Care ◽  
Tertiary Care ◽  
Cross Reactivity ◽  
Screening Tests ◽  
Zikv Infection ◽  
Igm Antibody ◽  
In Pregnancy

Abstract Background Zika Virus (ZIKV) infection in pregnancy is a major clinical concern. The CDC recommended that pregnant women living in an area with a ZIKV travel notice undergo ZIKV screening in the first and second trimesters of pregnancy. This study investigated the consequences of this screening on clinical management. Methods An IRB approved retrospective chart review was conducted using laboratory records of ZIKV testing on pregnant patients from January through December 2016 at multiple tertiary care centers in Miami, FL. Serum and/or urine samples were collected, based on CDC guidelines at the time, and evaluated for PCR and/or IgM evidence of ZIKV infection. Positive ZIKV PCR results indicated acute phase of infection. Previous infection was suggested by positive IgM antibody, but required confirmatory ZIKV plaque reduction neutralization testing (PRNT) testing due to IgM antibody cross reactivity with other flaviviruses. Results During 2016, 2,327 pregnant women were screened for ZIKV infection. At the peak in August 2016, 607 (26%) patients were tested and only 31 (5.1%) tests resulted within the month. Of those screened, 113 (4.85%) women tested positive for ZIKV PCR and/or IgM. In October 2016, 40 (35.4%) positive screening tests were received, the most positives resulting in a month. Confirmatory ZIKV PRNT testing was performed on those who were ZIKV IgM positive and PCR negative, with a total of 92 results received. Eighty-eight women were considered positive, 49 confirmed with positive titers (≥10). There were 28 women with negative titers (< 10), thus a false positive ZIKV screening rate of 30.4%, and 15 results were pending. Of women with false positive IgM screening, a median of 1 (range 0–4) additional ultrasound was done between receipt of the initial positive ZIKV screening and the subsequent receipt of the negative PRNT testing. Delays of results led to 21 (24%) positive tests reported after delivery and hospital discharge. Additionally, 18 (20.5%) women who tested PRNT positive had their originating sample drawn during admission for delivery with results available only after discharge. Conclusion Both delays in ZIKV testing results and false positive screening with ZIKV IgM led to challenges in counseling and clinical care of pregnant women living in an area of ongoing ZIKV transmission. Disclosures All authors: No reported disclosures.

scholarly journals Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S302-S303 ◽  
Author(s):  
Samantha Manuel ◽  
Liane Virginia-Cova ◽  
Loubiela Joseph ◽  
Chris Roggeveen ◽  
Radjin Steingrover
Keyword(s):  
Zika Virus ◽  
Cross Reactivity ◽  
Pregnant Female ◽  
Serum Samples ◽  
Zikv Infection ◽  
Igm Elisa ◽  
Pcr Diagnosis ◽  
Two Samples ◽  
Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

scholarly journals Autophagy in Zika Virus Infection: A Possible Therapeutic Target to Counteract Viral Replication

2019 ◽  
Vol 20 (5) ◽  
pp. 1048 ◽  
Author(s):  
Rossella Gratton ◽  
Almerinda Agrelli ◽  
Paola Tricarico ◽  
Lucas Brandão ◽  
Sergio Crovella
Keyword(s):  
Public Health ◽  
Viral Replication ◽  
Zika Virus ◽  
Health Concern ◽  
Mtor Signaling Pathway ◽  
Catabolic Pathway ◽  
Public Health Concern ◽  
Zikv Infection ◽  
Fundamental Process

Zika virus (ZIKV) still constitutes a public health concern, however, no vaccines or therapies are currently approved for treatment. A fundamental process involved in ZIKV infection is autophagy, a cellular catabolic pathway delivering cytoplasmic cargo to the lysosome for degradation—considered as a primordial form of innate immunity against invading microorganisms. ZIKV is thought to inhibit the Akt-mTOR signaling pathway, which causes aberrant activation of autophagy promoting viral replication and propagation. It is therefore appealing to study the role of autophagic molecular effectors during viral infection to identify potential targets for anti-ZIKV therapeutic intervention.

scholarly journals Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Angelica Cifuentes Kottkamp ◽  
Elfie De Jesus ◽  
Rebecca Grande ◽  
Julia A. Brown ◽  
Adam R. Jacobs ◽  
...  
Keyword(s):  
Viral Replication ◽  
Pregnant Women ◽  
Vulnerable Populations ◽  
Zika Virus ◽  
Ex Vivo ◽  
Pyrimidine Biosynthesis ◽  
Zikv Infection ◽  
Antiviral Therapies ◽  
Virion Production ◽  
Women And Children

ABSTRACT Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children. IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

scholarly journals Protective to a T: The Role of T Cells during Zika Virus Infection

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 820 ◽  
Author(s):  
Ryan D. Pardy ◽  
Martin J. Richer
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Zika Virus ◽  
Viral Infections ◽  
Cross Reactivity ◽  
Negative Effects ◽  
Cell Responses ◽  
Recent Emergence ◽  
Human Infections

CD4 and CD8 T cells are an important part of the host’s capacity to defend itself against viral infections. During flavivirus infections, T cells have been implicated in both protective and pathogenic responses. Given the recent emergence of Zika virus (ZIKV) as a prominent global health threat, the question remains as to how T cells contribute to anti-ZIKV immunity. Furthermore, high homology between ZIKV and other, co-circulating flaviviruses opens the possibility of positive or negative effects of cross-reactivity due to pre-existing immunity. In this review, we will discuss the CD4 and CD8 T cell responses to ZIKV, and the lessons we have learned from both mouse and human infections. In addition, we will consider the possibility of whether T cells, in the context of flavivirus-naïve and flavivirus-immune subjects, play a role in promoting ZIKV pathogenesis during infection.

scholarly journals Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 975 ◽  
Author(s):  
Kíssila Rabelo ◽  
Antônio José da Silva Gonçalves ◽  
Luiz José de Souza ◽  
Anna Paula Sales ◽  
Sheila Maria Barbosa de Lima ◽  
...  
Keyword(s):  
Mast Cells ◽  
Cell Line ◽  
Zika Virus ◽  
Post Infection ◽  
Immune Cell ◽  
Cell Types ◽  
Ultrastructural Changes ◽  
Congenital Defects ◽  
Zikv Infection ◽  
Intracellular Changes

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.

scholarly journals Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine

2020 ◽  
Author(s):  
Ran Wang ◽  
Zida Zhen ◽  
Lance Turtle ◽  
Baohua Hou ◽  
Yueqi Li ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Cellular Immunity ◽  
Zika Virus ◽  
T Cell Response ◽  
Encephalitis Virus ◽  
Cross Protection ◽  
World Health ◽  
Effective Vaccine ◽  
Zikv Infection

AbstractZika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection, but did mediate antibody dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue into developing a novel bivalent vaccine against both ZIKV and JEV.ImportanceJapanese encephalitis is a controllable disease in many countries in Asia, especially in China, where many people have Japanese encephalitis virus (JEV) immunity due to extensive JEV vaccination campaigns or natural exposure. Live-attenuated SA14-14-2 strain is a safe and effective vaccine recommended by the World Health Organization and has been vaccinated more than 600 million doses since 1989. As the prevalence of Zika virus (ZIKV) and rising risk in above regions, the cross-reactive immune response between these two antigenically closely related flaviviruses, JEV and ZIKV, should also be fully recognized, which is presumed to be based on those ambiguous cross-reactive immunity between dengue virus and ZIKV. In this study, we found that JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice, which is mainly due to cellular immunity rather than neutralizing antibody response. However, specific protective components or cooperation between components warrant to be explored in subsequent experiments. In conclusion, this study can provide important evidence for those who live in JEV-endemic areas and are at risk for ZIKV infection.

scholarly journals Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

2020 ◽  
Author(s):  
Theerut Densathaporn ◽  
Rassamee Sangthong ◽  
Monvaris Sakolnapa ◽  
Smonrapat Surasombatpattana ◽  
Marisa Kemapunmanus ◽  
...  
Keyword(s):  
General Population ◽  
Pregnant Women ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Zikv Infection ◽  
Factors Associated ◽  
Neutralizing Capacity ◽  
Southern Thailand ◽  
Outbreak Areas ◽  
Index Cases

Abstract Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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