Zika Virus Transmission Research Articles

Serological detection of Zika Virus infection among HIV infected pregnant women in Dutse, Jigawa State, Nigeria

Zika virus infection is one of the emerging often neglected viral infections in Africa. A study to determine the seroprevalence of Zika Virus (ZIKV) infection among HIV Positive Pregnant Women in Dutse, Jigawa state, Nigeria was conducted. A total of 89 HIV positive pregnant women were randomly selected for the study. Samples were collected between February, 2020 and March, 2021 from Rashid Shekoni specialist Hospital and Dutse General Hospital respectively. A standard rapid immuno-chromatographic technique that is; rapid ELISA was used to screen all the sera for IgM antibodies to Zika virus in addition to haematological analysis using Automated Haematological Analyser (Sysmex, KX-21N). Result has shown that out of the 89 participants enrolled, 4 (4.5%) of them were infected with Zika virus. Seventy-five Percent (75%) of the study participants had PCV below 30% and Lymphocytes below 20%. It was also found that, 75% of the participants that have Zika virus infection were in their first trimester of pregnancy. It can be concluded that, there is a low sero-prevalence of ZIKV infection in the study population. However, the need for public health authorities to provide quick response for the prevention of transmission of Zika virus in the state cannot be overemphasized. Hospital delivery among HIV positive pregnant women co-infected with Zika virus should be encouraged in Jigawa State to prevent vertical transmission to their babies.

The Innate Defense in the Zika-Infected Placenta.

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family, genus Flavivirus and was first isolated 1947 in Uganda, Africa, from the serum of a sentinel Rhesus monkey. Since its discovery, the virus was responsible for major outbreaks in several different countries, being linked to severe complications in pregnant women, neonatal birth defects and the congenital zika syndrome. Maternal-fetal transmission of ZIKV can occur in all trimesters of pregnancy, and the role of the placenta and its cells in these cases is yet to be fully understood. The decidua basalis and chorionic villi, maternal-fetal components of the placenta, contain a rich immunological infiltrate composed by Hofbauer cells, mastocytes, dendritic cells and macrophages, primary cells of the innate immune response that have a role that still needs to be better investigated in ZIKV infection. Recent studies have already described several histopathological features and the susceptibility and permissiveness of placenta cells to infection by the Zika virus. In this review, we address some of the current knowledge on the innate immune responses against ZIKV, especially in the placenta.

Adaptation of Essential Care for Every Baby educational program to improve infant outcomes in the context of Zika

BackgroundThe outbreak and ongoing transmission of Zika virus provided an opportunity to strengthen essential newborn care and early childhood development systems through collaboration with the US Agency for International Development Applying Science to Strengthen and Improve Systems (USAID ASSIST). The objective was to create a system of sustainable training dissemination which improves newborn care-related quality indicators in the context of Zika.MethodsFrom 2018–19, USAID ASSIST supported a series of technical assistance visits by the American Academy of Pediatrics (AAP) in four Caribbean countries to strengthen the clinical capacity in care of children potentially affected by Zika through dissemination of Essential Care for Every Baby (ECEB), teaching QI methodology, coaching visits, and development of clinical care guidelines. ECEB was adapted to emphasize physical exam findings related to Zika. The first series of workshops were facilitated by AAP technical advisors and the second series were facilitated by the newly trained local champions. Quality of care was monitored with performance indicators at 134 health facilities.ResultsA repeated measures (pre-post) ANOVA was conducted, revealing significant pre-post knowledge gains [F(1) = 197.9, p < 0.001] on knowledge check scores. Certain performance indicators related to ECEB practices demonstrated significant changes and midline shift on the run chart in four countries.ConclusionECEB can be adapted to incorporate important local practices, causes of neonatal morbidity and mortality, and differing healthcare system structures, which, as one part of a larger technical assistance package, leads to improved performance of health systems.

Methodological procedures explain observed differences in the competence of European populations of Aedes albopictus for the transmission of Zika virus

The risk of autochthonous transmission of Zika virus (ZIKV) in Europe greatly depends on the capacity of Aedes albopictus to transmit ZIKV. Experimental studies of the vector competence of European populations of this invasive mosquito species provided contrasting results, that may suggest differences between mosquito populations in ZIKV competence and/or differences in the methodological procedures used on the experimental studies. We systematically reviewed published studies of experimental mosquito infections and show that differences detected in the infection and transmission rates of Ae. albopictus are mostly due to differences between studies in the temperature, the viral load used to inoculate mosquitoes, and the number of days post-exposure (dpe) to the virus at which mosquitoes were analysed. In particular, the proportion of infected mosquitoes was affected by the viral load inoculated and the dpe, whereas the transmission rate was influenced by the viral load and temperature. Thus, the methodological differences used in these studies greatly affect the conclusions obtained regarding the role of Ae. albopictus in Europe as a competent vector for ZIKV and its epidemiological relevance.

Brazilian Populations of Aedes aegypti Resistant to Pyriproxyfen Exhibit Lower Susceptibility to Infection with Zika Virus.

Zika virus (ZIKV) infection has caused devastating consequences in Brazil as infections were associated with neurological complications in neonates. Aedes aegypti is the primary vector of ZIKV, and the evolution of insecticide resistance (IR) in this species can compromise control efforts. Although relative levels of phenotypic IR in mosquitoes can change considerably over time, its influence on vector competence for arboviruses is unclear. Pyriproxyfen (PPF)-resistant populations of Ae. aegypti were collected from five municipalities located in Northeast of Brazil, which demonstrated different resistance levels; low (Serrinha, Brumado), moderate (Juazeiro do Norte, Itabuna), and high (Quixadá). Experimental per os infection using ZIKV were performed with individuals from these populations and with an insecticide susceptible strain (Rockefeller) to determine their relative vector competence for ZIKV. Although all populations were competent to transmit ZIKV, mosquitoes derived from populations with moderate to high levels of IR exhibited similar or lower susceptibility to ZIKV infection than those from populations with low IR or the susceptible strain. These observations suggest an association between IR and arbovirus infection, which may be attributable to genetic hitchhiking. The use of PPF to control Brazilian Ae. aegypti may be associated with an indirect benefit of reduced susceptibility to infection, but no changes in disseminated infection and transmission of ZIKV among PPF-resistant phenotypes.

Dynamics of a Zika virus transmission model with seasonality and periodic delays

Zika virus is an arbovirus transmitted by mosquitoes, which can cause low fever, mild skin rash and eye swelling. In severe cases, it may cause neurological and autoimmune complications, such as microcephaly. Climate factors and weather, especially temperature, have a strong effect on the transmission dynamics of vector-borne diseases, such as Dengue, West Nile virus, Schistosomiasis, and Zika. To study the comprehensive effects of spatial structure, seasonality and the temperature sensitivity of incubation period on the transmission of Zika virus, we propose a PDE model with periodic delay. We present the basic reproduction number R0 and explore the global dynamics of the model. Our simulations show that (i) it is possible to overestimate R0 in the periodic system if the spatial averaged system is used; (ii) R0 can be underestimated in the absence of seasonality; and (iii) shortening the incubation period may reduce the risk of disease transmission, which is critical for modeling the transmission of Zika virus dynamics to understand geographic and seasonal limits of Zika risk.

Aerosolized Zika virus infection in Guinea pigs

ABSTRACT Zika virus (ZIKV) is primarily transmitted through mosquito bites and sexual contact, and vertical transmission of ZIKV has also been observed in humans. In addition, ZIKV infection via unknown transmission routes has been frequently reported in clinical settings. However, whether ZIKV can be transmitted via aerosol routes remains unknown. In this study, we demonstrated that aerosolized ZIKV is fully infectious in vitro and in vivo. Remarkably, intratracheal (i.t.) inoculation with aerosolized ZIKV led to rapid viremia and viral secretion in saliva, as well as robust humoral and innate immune responses in guinea pigs. Transcriptome analysis further revealed that the expression of genes related to viral processes, biological regulation and the immune response was significantly changed. Together, our results confirm that aerosolized ZIKV can result in systemic infection and induce both innate and adaptive immune responses in guinea pigs, highlighting the possibility of ZIKV transmission via aerosols.

Abstract 27 Limitations of Current Human Cell, Tissue, and Cellular-based Product Donor Eligibility Guidance: Analyzing the Impact on a Large Public Cord Blood Bank

IntroductionCord blood (CB) is considered a human cell, tissue, and cellular-based product (HCT/P) by the U.S. Food and Drug Administration (FDA) and is licensed through a Biological Licensing Application (BLA). Cord blood units (CBUs) require less precise donor tissue matching than other stem cell sources, which increases their availability for racial/ethnic minorities. However, a small percentage of banked CBUs are used for transplants. Updating FDA donor eligibility guidance may expand licensed CBU supply and cord blood bank (CBB) sustainability.ObjectiveThe objectives of this study were to analyze the impact of Zika virus (ZIKV) donor screening recommendations on the licensing status of banked CBUs and to propose updated policy recommendations.MethodsA retrospective analysis of Carolinas Cord Blood Bank (CCBB) data (from January 2016 to May 2022) was performed to describe CBU eligibility and shipment status. Qualitative comparisons of FDA guidance to reduce the risk of relevant communicable diseases were completed for blood versus HCT/P.Results CCBB: 8,877 banked CBUs from 2016-2022 (85.3% licensed; 14.7% unlicensed) (Table 1). 4,361 (49.1%) of CBUs were from Caucasian donors and 1,349 (15.2%) were from African American donors. 689 (52.7%) CBUs were unlicensed due to ZIKV risk. The number of CBUs with ZIKV risk banked annually has decreased significantly since 2020, with 174 ZIKV-risk CBUs in 2020 versus 63 in 2021. 26 unlicensed CBUs collected in 2016 or later have been infused versus 210 licensed CBUs. 7 unlicensed, infused CBUs had identified ZIKV risk. No ZIKV transmission was reported from these transplants. FDA Guidance: HCT/P ZIKV recommendations have not been updated since 2018 despite FDA removal of ZIKV from the relevant transfusion-transmitted infections in 2021. Recommendations for minimizing transfusion-transmission risk of human immunodeficiency virus (HIV) and variant Creutzfeldt-Jakob disease (vCJD) were updated in 2020 and 2022, respectively, to increase blood supply. New vCJD guidance eliminated geographic risk-related donor restrictions.Table 1.Characteristics of CBUs banked at CCBB January 2016 to May 2022CBU StatusNumber of Units (%)Banked8,877 (100%) Banked, licensed7,569 (85.3%) Banked, unlicensed1,308 (14.7%) Banked with ZIKV risk (travel-related donor deferral)689 (7.8%) Banked with Hepatitis B core antibody positive82 (<1.0%)Infused236/8,877 (2.7%) Infused, licensed210 (89.0 %) Infused, unlicensed26 (11.0%) Infused, Caucasian donor134 (56.8%) Infused, African American donor28 (11.9%) Infused, unlicensed with ZIKV risk7/26 (26.9%) Infused, unlicensed with Hepatitis B core antibody positive3/26 (11.5%)DiscussionGuidance for reducing disease transmission for blood and blood components have recently been updated to increase blood supply. The FDA must consider new data to revise the HCT/P donor screening recommendations. Adopting these changes will increase the number of HCT/P donors, the quantity of licensed CBUs, and potentially improve access to cellular therapies for a more diverse patient population.

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika.

Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22 U.S. states and territories, January 2016 to June 2017.

During the Centers for Disease Control and Prevention's Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016 to June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared with areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January-March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR=12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3 [4.7, 18.4]), and cerebral/cortical atrophy (6.7 [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

Interferon Epsilon Signaling Confers Attenuated Zika Replication in Human Vaginal Epithelial Cells.

Zika virus (ZIKV) is an emerging flavivirus that causes congenital birth defects and neurological compilations in the human host. Although ZIKV is primarily transmitted through infected mosquitos, recent studies reveal sexual contact as a potential transmission route. In vagina-bearing individuals, the vaginal epithelium constitutes the first line of defense against viruses. However, it is unclear how ZIKV interacts with the vaginal epithelium to initiate ZIKV transmission. In this study, we demonstrate that exposing ZIKV to human vaginal epithelial cells (hVECs) resulted in de novo viral RNA replication, increased envelope viral protein production, and a steady, extracellular release of infectious viral particles. Interestingly, our data show that, despite an increase in viral load, the hVECs did not exhibit significant cytopathology in culture as other cell types typically do. Furthermore, our data reveal that the innate antiviral state of hVECs plays a crucial role in preventing viral cytopathology. For the first time, our data show that interferon epsilon inhibits ZIKV replication. Collectively, our results in this study provide a novel perspective on the viral susceptibility and replication dynamics during ZIKV infection in the human vaginal epithelium. These findings will be instrumental towards developing therapeutic agents aimed at eliminating the pathology caused by the virus.

Wolbachia wPip Blocks Zika Virus Transovarial Transmission in Aedes albopictus.

ABSTRACTWolbachia is being developed as a biological tool to suppress mosquito populations and/or interfere with their transmitted viruses. Adult males with an artificial Wolbachia infection have been released, successfully yielding population suppression in multiple field trials. The main characteristic of the artificial Wolbachia-infected mosquitoes used in the suppression program is the lower vector competence than that in native infected/uninfected mosquitoes in horizontal and vertical transmission. Our previous studies have demonstrated that the Aedes albopictus HC line infected with a trio of Wolbachia strains exhibited almost complete blockade of dengue virus (DENV) and Zika virus (ZIKV) in horizontal and vertical transmission. However, the extent to which Wolbachia inhibits virus transovarial transmission is unknown since no studies have been performed to determine whether Wolbachia protects ovarian cells against viral infection. Here, we employed ovarian cells of the Ae. albopictus GUA (a wild-type mosquito line superinfected with two native Wolbachia strains, wAlbA and wAlbB), HC, and GT lines (tetracycline-cured, Wolbachia-uninfected mosquitoes), which exhibit key traits, and compared them to better understand how Wolbachia inhibits ZIKV transovarial transmission. Our results showed that the infection rate of adult GT progeny was significantly higher than that of GUA progeny during the first and second gonotrophic cycles. In contrast, the infection rates of adult GT and GUA progeny were not significantly different during the third gonotrophic cycle. All examined adult HC progeny from three gonotrophic cycles were negative for ZIKV infection. A strong negative linear correlation existed between Wolbachia density and ZIKV load in the ovaries of mosquitoes. Although there is no obvious coexistence area in the ovaries for Wolbachia and ZIKV, host immune responses may play a role in Wolbachia blocking ZIKV expansion and maintenance in the ovaries of Ae. albopictus. These results will aid in understanding Wolbachia-ZIKV interactions in mosquitoes.IMPORTANCE Area-wide application of Wolbachia to suppress mosquito populations and their transmitted viruses has achieved success in multiple countries. However, the mass release of Wolbachia-infected male mosquitoes involves a potential risk of accidentally releasing fertile females. In this study, we employed ovarian cells of the Ae. albopictus GUA, HC, and GT lines, which exhibit key traits, and compared them to better understand how Wolbachia inhibits ZIKV transovarial transmission. Our results showed an almost complete blockade of ZIKV transmission in HC female mosquitoes. Wolbachia in natively infected GUA mosquitoes negative affected ZIKV, and this interference was shown by slightly lower loads than those in HC mosquitoes. Overall, our work helps show how Wolbachia blocks ZIKV expansion and maintenance in the ovaries of Ae. albopictus and aids in understanding Wolbachia-ZIKV interactions in mosquitoes.

Model-Based Projection of Zika Infection Risk with Temperature Effect: A Case Study in Southeast Asia.

Zika virus (ZIKV) recently reemerged in the Americas and rapidly expanded in global range. It is posing significant concerns of public health due to its link to birth defects and its complicated transmission routes. Southeast Asia is badly hit by ZIKV, but limited information was found on the transmission potential of ZIKV in the region. In this paper, we develop a new dynamic process-based mathematical model, which incorporates the interactions among humans (sexual transmissibility), and between human and mosquitoes (biting transmissibility), as well as the essential impacts of temperature. The model is first validated by fitting the 2016 ZIKV outbreak in Singapore via Markov chain Monte Carlo method. Based on that, we demonstrate the effects of temperature on mosquito ecology and ZIKV transmission, and further clarify the potential risk of ZIKV outbreak in Southeast Asian countries. The results show that (i) the estimated infection reproduction number [Formula: see text] in Singapore fell from 6.93 (in which the contribution of sexual transmission was 0.89) to 0.24 after the deployment of control strategies; (ii) the optimal temperature for the reproduction of ZIKV infections and adult mosquitoes are estimated to be [Formula: see text]C and [Formula: see text]C, respectively; and (iii) the [Formula: see text] in Southeast Asia could be between 3 and 7, with an inverted-U shape around the year. The large values of [Formula: see text] and the simulative patterns of ZIKV transmission in each country highlights the high risk of ZIKV attack in Southeast Asia.

Serological evidence of possible high levels of undetected transmission of Zika virus among Papua New Guinea military personnel, 2019

The Papua New Guinea (PNG) Health Department retrospectively reported six cases of Zika virus (ZIKV) from a cohort of febrile patients during outbreaks of dengue and malaria in 2016. However, the transmission of ZIKV remains unclear due to lack of testing capability. This study aimed to determine the level of immunity to ZIKV among PNG military personnel (PNGMP) in 2019. Sera of 208 PNGMP recruited in April 2019 was tested for the presence of anti-ZIKV immunoglobulin G (IgG) and M (IgM) antibodies using Euroimmun IgG/IgM detection kits, and anti-ZIKV neutralizing antibody (Nab) against a ZIKV African strain on all anti-ZIKV-IgG/IgM+ samples. Anti-ZIKV seropositivity of these sera was as follows: IgG, 67%; IgM, 9%; and Nab, 65%. Five of 19 anti-ZIKV-IgM+ samples had anti-ZIKV-Nab titres ≥20, as well as an anti-ZIKV-Nab titre ratio ≥4 compared with the Nab titres of four anti-dengue serotypes, so met the criteria of the World Health Organization (WHO) for confirmed ZIKV infection. The prevalence of anti-ZIKV-Nab of 65% suggests that there are high levels of ZIKV exposure among PNGMP. Five of the 19 anti-ZIKV-IgM+ samples met the WHO criteria for confirmed ZIKV infection, suggesting a recent undetected outbreak in PNGMP. These results provide better understanding of the current ZIKV epidemic status in PNGMP.

The fetal lineage is susceptible to Zika virus infection within days of fertilization.

ABSTRACTAdults contracting Zika virus (ZIKV) typically exhibit mild symptoms, yet ZIKV infection of pregnant individuals can cause miscarriage or birth defects in their offspring. Many studies have focused on maternal-to-fetal ZIKV transmission via blood and placenta. Notably, however, ZIKV is also transmitted sexually, raising the possibility that ZIKV could infect the embryo shortly after fertilization, long before the placenta is established. Here, we evaluate the consequences of ZIKV infection in mouse embryos during the first few days of embryogenesis. We show that divergent strains of ZIKV can infect the fetal lineage and can cause developmental arrest, raising concern for the developmental consequences of sexual ZIKV transmission.This article has an associated ‘The people behind the papers’ interview.

The people behind the papers – Jennifer Watts and Amy Ralston

Zika virus infection during pregnancy can have severe consequences for fetal development and survival. A new paper in Development investigates whether sexually transmitted Zika virus could infect preimplantation embryos and dissects the impact of infection at this stage. We caught up with first author, Jennifer Watts, and corresponding author, Amy Ralston, a professor at Michigan State University, to find out more about their research.

Survival and Replication of Zika Virus in Diapause Eggs of Aedes Albopictus From Beijing, China

Zika virus (ZIKV) has emerged as a globally important arbovirus. The virus is primarily transmitted to humans through the bite of an infective Aedes albopictus in temperate area. Vertical transmission of ZIKV by Ae. albopictus is determined and has been suggested to be a means by which the virus could persist in nature. Ae. albopictus undergoes a well-characterized photoperiodic diapause. Viruses are harbored by overwintering mosquitoes in diapause that contributes to the resurgence of vertebrate diseases in the following spring, yet little is known about the impact of diapause on the regulation of viral replication and survival. The purpose of this study is to determine that Ae. albopictus in Beijing are highly susceptible to ZIKV (92.3%), and viable virus is passed to their organs of progeny via vertical transmission. Moreover, diapause eggs (diapause incidence 97.8%) had significantly lower minimum infection rates and filial infection rates of the first gonotrophic cycle than those of the second gonotrophic cycle in the short-day photoperiod group. Regarding the development of diapause eggs, the minimum infection rates and ZIKV RNA copy number increased significantly, suggesting that virus RNA replication occurred in the diapause eggs. Meanwhile, eggs from the ZIKV-infected mosquitoes had a significantly lower hatching rate compared with uninfected mosquitoes, implying an intriguing interaction between diapause eggs and virus. The findings here suggest that vertical transmission of ZIKV from diapause eggs to progeny may have a critical epidemiological role in the dissemination and maintenance of ZIKV circulating in the vector.

Zika virus-like particle vaccine fusion loop mutation increases production yield but fails to protect AG129 mice against Zika virus challenge.

Zika virus (ZIKV) is a mosquito-borne flavivirus with maternal infection associated with preterm birth, congenital malformations, and fetal death, and adult infection associated with Guillain-Barré syndrome. Recent widespread endemic transmission of ZIKV and the potential for future outbreaks necessitate the development of an effective vaccine. We developed a ZIKV vaccine candidate based on virus-like-particles (VLPs) generated following transfection of mammalian HEK293T cells using a plasmid encoding the pre-membrane/membrane (prM/M) and envelope (E) structural protein genes. VLPs were collected from cell culture supernatant and purified by column chromatography with yields of approximately 1-2mg/L. To promote increased particle yields, a single amino acid change of phenylalanine to alanine was made in the E fusion loop at position 108 (F108A) of the lead VLP vaccine candidate. This mutation resulted in a modest 2-fold increase in F108A VLP production with no detectable prM processing by furin to a mature particle, in contrast to the lead candidate (parent). To evaluate immunogenicity and efficacy, AG129 mice were immunized with a dose titration of either the immature F108A or lead VLP (each alum adjuvanted). The resulting VLP-specific binding antibody (Ab) levels were comparable. However, geometric mean neutralizing Ab (nAb) titers using a recombinant ZIKV reporter were significantly lower with F108A immunization compared to lead. After virus challenge, all lead VLP-immunized groups showed a significant 3- to 4-Log10 reduction in mean ZIKV RNAemia levels compared with control mice immunized only with alum, but the RNAemia reduction of 0.5 Log10 for F108A groups was statistically similar to the control. Successful viral control by the lead VLP candidate following challenge supports further vaccine development for this candidate. Notably, nAb titer levels in the lead, but not F108A, VLP-immunized mice inversely correlated with RNAemia. Further evaluation of sera by an in vitro Ab-dependent enhancement assay demonstrated that the F108A VLP-induced immune sera had a significantly higher capacity to promote ZIKV infection in FcγR-expressing cells. These data indicate that a single amino acid change in the fusion loop resulted in increased VLP yields but that the immature F108A particles were significantly diminished in their capacity to induce nAbs and provide protection against ZIKV challenge.

HLA-G, LILRB1 and LILRB2 Variants in Zika Virus Transmission from Mother to Child in a Population from South and Southeast of Brazil.

During the 2015–2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother–fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother–fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother–child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates’ correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases.

Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.