Route Of Vertical Transmission Research Articles

The existence of sodium taurocholate co-transporting polypeptide and Hepatitis B replication markers on the placenta suggests: Another home for the virus

Background and Aim: The transplacental routes of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Although, several serological studies have reported the presence of HBV antigens in placenta, no study has documented placental replication of HBV yet. Here we present evidence which suggest HBV can replicate in placenta.

Stability and optimal control of a disease model with vertical transmission and saturated incidence

This paper studies a nonlinear SI-model featuring vertical transmission and saturated incidence terms. The model is analyzed by utilizing some dynamical system tools to assess the dynamic behavior of solutions to a system of first order nonlinear ordinary differential equations arising from the spread of a vertically transmitted disease in a population. The mathematical well-posedness of the governing model is proven through positivity and boundedness properties of solutions. Lyapunov functions with LaSalle’s invariance principle are used to establish the global asymptotic dynamics of the system about the disease-free and endemic steady states. Additionally, sensitivity analysis is conducted to show how the epidemiological threshold (basic reproduction number) of the model is affected by variations in parameters. The study is extended to explore the significance of a time-dependent optimal control for blocking vertical transmission route using Pontryagin’s maximum principle of the optimal control theory. The obtained qualitative results are supplemented by numerical simulations. It is shown that incorporation of the optimal control helps in preventing vertical transmission of infection, and in turn diminishes the spread of the disease in the population.

The Gut Microbiota of the Insect Infraorder Pentatomomorpha (Hemiptera: Heteroptera) for the Light of Ecology and Evolution.

The stinkbugs of the infraorder Pentatomomorpha are a group of important plant sap-feeding insects, which host diverse microorganisms. Some are located in their complex morphological midgut compartments, while some within the specialized bacteriomes of insect hosts. This perpetuation of symbioses through host generations is reinforced via the diverse routes of vertical transmission or environmental acquisition of the symbionts. These symbiotic partners, reside either through the extracellular associations in midgut or intracellular associations in specialized cells, not only have contributed nutritional benefits to the insect hosts but also shaped their ecological and evolutionary basis. The stinkbugs and gut microbe symbioses present a valuable model that provides insights into symbiotic interactions between agricultural insects and microorganisms and may become potential agents for insect pest management.

Brazilian Protocol for Sexually Transmitted Infections 2020: Zika virus infection.

This article addresses the vector, sexual and vertical transmissions of the Zika virus, a topic covered in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Although in Brazil Zika virus is transmitted more predominantly by Aedes aegypti, the vertical and sexual transmission routes are of significant importance for reproductive health. Sexual transmission demands specific prophylactic interventions, including the use of male or female condoms, especially among couples in a risk situation and planning pregnancy. Vertical transmission is linked to severe structural abnormalities of the central nervous system, and there is still no vaccine or known pharmacological resources that can prevent it. As the disease is predominantly asymptomatic, failure to comply with the basic principles of care and guidelines associated with the spread of the infection transcends the severity of the disease's symptoms.

Pharyngeal sampling for PCR-testing in the investigation of SARS-COV-2 vertical transmission in pregnancy

The novel COVID-19 global pandemic has raised, among many others, major concerns regarding the impact of infection during pregnancy. At the time of this writing, vertical SARS-COV-2 transmission in pregnancy has been considered probable, but is yet to be confirmed. According to the published reports of infants born to COVID-19-affected mothers, as well as the anecdotal experience of current practices worldwide, it appears that investigations regarding the possibility of SARS-COV-2 vertical transmission in pregnancy have so far been based, to a large extent, on PCR testing of neonatal pharyngeal swab samples. Given that the hypothetical route of vertical transmission for SARS-COV-2 is less likely to involve the upper respiratory tract, contrary to what happens after birth, it would be advisable to include appropriate biological samples, such as cord blood, placenta, amniotic fluid and neonatal blood, along with the pharyngeal samples, in order to contribute significantly to such investigations. Revision and enhancement of the so far prevailing practices appear even more important, as the impact of SARS-COV-2 infection occurring early in pregnancy is still unknown, this challenge remaining to be confronted in the immediate future.

Tissue Tropisms and Transstadial Transmission of a Rickettsia Endosymbiont in the Highland Midge, Culicoides impunctatus (Diptera: Ceratopogonidae).

Rickettsia is a genus of intracellular bacteria which can manipulate host reproduction and alter sensitivity to natural enemy attack in a diverse range of arthropods. The maintenance of Rickettsia endosymbionts in insect populations can be achieved through both vertical and horizontal transmission routes. For example, the presence of the symbiont in the follicle cells and salivary glands of Bemisia whiteflies allows Belli group Rickettsia transmission via the germ line and plants, respectively. However, the transmission routes of other Rickettsia bacteria, such as those in the Torix group of the genus, remain underexplored. Through fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) screening, this study describes the pattern of Torix Rickettsia tissue tropisms in the highland midge, Culicoides impunctatus (Diptera: Ceratopogonidae). Of note is the high intensity of infection of the ovarian suspensory ligament, suggestive of a novel germ line targeting strategy. Additionally, localization of the symbiont in tissues of several developmental stages suggests transstadial transmission is a major route for ensuring maintenance of Rickettsia within C. impunctatus populations. Aside from providing insights into transmission strategies, the presence of Rickettsia bacteria in the fat body of larvae indicates potential host fitness and vector capacity impacts to be investigated in the future.IMPORTANCE Microbial symbionts of disease vectors have garnered recent attention due to their ability to alter vectorial capacity. Their consideration as a means of arbovirus control depends on symbiont vertical transmission, which leads to spread of the bacteria through a population. Previous work has identified a Rickettsia symbiont present in several species of biting midges (Culicoides spp.), which transmit bluetongue and Schmallenberg arboviruses. However, symbiont transmission strategies and host effects remain underexplored. In this study, we describe the presence of Rickettsia in the ovarian suspensory ligament of Culicoides impunctatus Infection of this organ suggests the connective tissue surrounding developing eggs is important for ensuring vertical transmission of the symbiont in midges and possibly other insects. Additionally, our results indicate Rickettsia localization in the fat body of Culicoides impunctatus As the arboviruses spread by midges often replicate in the fat body, this location implies possible symbiont-virus interactions to be further investigated.

Stability of the Virome in Lab- and Field-Collected Aedes albopictus Mosquitoes across Different Developmental Stages and Possible Core Viruses in the Publicly Available Virome Data of Aedes Mosquitoes.

Aedes mosquitoes can efficiently transmit many pathogenic arboviruses, placing a great burden on public health worldwide. In addition, they also carry a number of insect-specific viruses (ISVs), and it was recently suggested that some of these ISVs might form a stable species-specific "core virome" in mosquito populations. However, little is known about such a core virome in laboratory colonies and if it is present across different developmental stages. In this study, we compared the viromes in eggs, larvae, pupae, and adults of Aedes albopictus mosquitoes collected from a lab colony and compared each to the virome of different developmental stages collected in the field. The virome in lab-derived A. albopictus was very stable across all stages, consistent with a vertical transmission route of these viruses, and formed a possible "vertically transmitted core virome." The different stages of field-collected A. albopictus mosquitoes also contained this stable vertically transmitted core virome, as well as another set of viruses (e.g., viruses distantly related to Guadeloupe mosquito virus, Hubei virga-like virus 2, and Sarawak virus) shared by mosquitoes across different stages, which might represent an "environment-derived core virome." To further study this core set of ISVs, we screened 48 publicly available SRA viral metagenomic data sets of mosquitoes belonging to the genus Aedes, showing that some of the identified ISVs were identified in the majority of SRAs and providing further evidence supporting the core-virome concept.IMPORTANCE Our study revealed that the virome was very stable across all developmental stages of both lab-derived and field-collected Aedes albopictus The data representing the core virome in lab A. albopictus proved the vertical transmission route of these viruses, forming a "vertically transmitted core virome." Field mosquitoes also contained this stable vertically transmitted core virome as well as additional viruses, which probably represented "environment-derived core virome" and which therefore were less stable over time and geography. By further screening publicly available SRA viral metagenomic data sets from mosquitoes belonging to the genus Aedes, some of the identified core ISVs were shown to be present in the majority of SRAs, such as Phasi Charoen-like phasivirus and Guadeloupe mosquito virus. How these core ISVs influence the biology of the mosquito host and arbovirus infection and evolution deserves to be further explored.

Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS.

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is highly infectious and its ongoing outbreak has been declared a global pandemic by the WHO. Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. The intrauterine vertical transmission potential of SARS-CoV-2 also remains controversial. Herein, we discuss the potential effect of COVID-19 on maternal and infant outcomes based on current studies, including those published in Chinese, in a total of 80 mothers with COVID-19 and 80 infants. We also comprehensively explored the mother-to-child transmission routes of SARS-CoV-2, in particular the route of intrauterine vertical transmission. Given SARS-CoV-2 is a sister to SARS-CoV, of the SARS-related coronavirus species, we made a comprehensive comparison between them to learn from experiences with SARS. Although there is no evidence supporting the intrauterine vertical transmission of SARS-CoV-2, our comprehensive analysis suggests that the adverse maternal and infant outcomes caused by COVID-19 cannot be underestimated. Further, we speculated that the inconsistency between nucleic acids and serological characteristics IgM to SARS-CoV-2 of infants' specimens may be caused by the disruption of the amniotic barrier by the inflammatory factors induced by SARS-CoV-2 infection. Our review is beneficial to understand the effect of SARS-CoV-2 on maternal and infant outcomes.

Management of mother–newborn dyads in the COVID-19 era

Management of mother–newborn dyads in the COVID-19 era

Large Overlap Between the Intestinal and Reproductive Tract Microbiomes of Chickens.

Recent work characterized the chicken reproductive tract (oviduct) microbiome composition and its similarity to the egg and chick microbiomes. However, the origin of the oviduct microbiome has not been addressed yet. Here, we characterized the microbiome composition along the oviduct (infundibulum, magnum, and shell gland) as well as in the gut (jejunum and cecum) of broiler breeders at 37 weeks of age of the Cobb industrial breed. We found that while the microbiome composition along the oviduct is similar, the three sites, jejunum, cecum, and oviduct hold distinct microbiomes. However, there was also a large overlap in the composition of the gut and oviduct microbiomes, with 55 and 53% of amplicon sequence variants (ASVs) representing 96 and 90% of the total abundance in the jejunum and cecum, respectively, shared with the magnum. Furthermore, we identified a strong correlation between the relative abundance of ASVs in the gut and their probability to be found in the oviduct. These results suggest that material from the gut travels the full length of the oviduct. This is possibly the result of chicken physiology which includes the cloaca, a cavity to which both the intestinal and reproductive tracts open into. As the cloaca is common to birds, reptiles, amphibians, most fish, and monotremes, our finding may be relevant to many vertebrates. Importantly, these results indicate that mere presence in, and ascending of the oviduct are not virulence characteristics specific to pathogens, as commonly thought, but are the result of chicken physiology and characterize all gut bacteria. Furthermore, whereas a vertical transmission route from the hen to the chick has been suggested, our work starts laying a mechanistic foundation to this route, by describing the movement of gut bacteria to the oviduct, where they may be enclosed in the developing egg. Last, as our results show that gut material travels the full length of the oviduct, fertilization in poultry occurs in the presence of at least bacterial products if not live bacteria, and therefore food additives, probiotics, and diet possibly have a much more direct effect on reproduction and egg formation than previously considered.

Transmission routes of 2019-novel coronavirus (2019-nCoV)

Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.

The chemokines CCL2 and CXCL10 produced by bovine endometrial epithelial cells induce migration of bovine B lymphocytes, contributing to transuterine transmission of BLV infection

Bovine leukemia virus (BLV) causes a lymphoproliferative disease in cattle and is transmitted horizontally and vertically via infected lymphocytes. Although transplacental infection is considered the predominant route of vertical transmission of BLV, the molecular mechanisms of this process remain to be elucidated. Notably, how BLV passes through the blood-placental barrier remains unclear, given that BLV is transmitted primarily by cell-to-cell contact. One hypothesis is that B cell migration to the placenta may be induced by certain endometrium-expressed chemokines. To test this hypothesis, we performed an in vitro cell migration assay using bovine B cell lines and endometrial epithelial cells. Cell migration assays showed that two bovine B cell lines, BL2M3 and BL3.1 cells, were attracted to the supernatant of bovine endometrial epithelial cells (BEnEpCs). Quantitative real-time RT-PCR showed that expression levels of mRNAs encoding the chemokines CCL2 and CXCL10 were higher in BEnEpCs than in MDBK cells. Additionally, an inhibition assay using immune serum against CCL2 and CXCL10 showed suppression of migration of bovine B cell lines. A syncytium assay showed that cells expressing BLV envelope (Env) protein fused with BEnEpCs. Here we found that bovine B cells are attracted by chemokines produced in the endometrium and that cells expressing BLV Env protein fused with endometrium epithelial cells. These results explain part of the molecular mechanism of transplacental transmission during BLV infection, although further analysis will be required. Advances in these areas are expected to contribute to controlling the spread of BLV.

Microsporidian infections in the species complex Gammarus roeselii (Amphipoda) over its geographical range: evidence for both host\u2013parasite co-diversification and recent host shifts

BackgroundMicrosporidians are obligate endoparasites infecting taxonomically diverse hosts. Both vertical (from mother to eggs) and horizontal (between conspecifics or between species) transmission routes are known. While the former may promote co-speciation and host-specificity, the latter may promote shifts between host species. Among aquatic arthropods, freshwater amphipod crustaceans are hosts for many microsporidian species. However, despite numerous studies, no general pattern emerged about host specificity and co-diversification. In south-eastern Europe, the gammarid Gammarus roeselii is composed of 13 cryptic lineages of Miocene to Pleistocene age but few genotypes of one lineage have spread postglacially throughout north-western Europe. Based on nearly 100 sampling sites covering its entire range, we aim to: (i) explore the microsporidian diversity present in G. roeselii and their phylogenetic relationships, especially in relation to the parasites infecting other Gammaridae; (ii) test if the host phylogeographical history might have impacted host–parasite association (e.g. co-diversifications or recent host shifts from local fauna).MethodsWe used part of the small subunit rRNA gene as source of sequences to identify and determine the phylogenetic position of the microsporidian taxa infecting G. roeselii.ResultsMicrosporidian diversity was high in G. roeselii with 24 detected haplogroups, clustered into 18 species-level taxa. Ten microsporidian species were rare, infecting a few individual hosts in a few populations, and were mostly phylogenetically related to parasites from other amphipods or various crustaceans. Other microsporidians were represented by widespread genera with high prevalence: Nosema, Cucumispora and Dictyocoela. Two contrasting host association patterns could be observed. First, two vertically transmitted microsporidian species, Nosema granulosis and Dictyocoela roeselum, share the pattern of infecting G. roeselii over most of its range and are specific to this host suggesting the co-diversification scenario. This pattern contrasted with that of Dictyocoela muelleri, the three species of Cucumispora, and the rare parasites, present only in the recently colonised region by the host. These patterns suggest recent acquisitions from local host species, after the recent spread of G. roeselii.ConclusionsMicrosporidians infecting G. roeselii revealed two scenarios of host–parasite associations: (i) ancient associations with vertically transmitted parasites that probably co-diversified with their hosts, and (ii) host shifts from local host species, after the postglacial spread of G. roeselii.

Drivers and patterns of microbial community assembly in a Lyme disease vector.

Vector‐borne diseases constitute a major global health burden and are increasing in geographic range and prevalence. Mounting evidence has demonstrated that the vector microbiome can impact pathogen dynamics, making the microbiome a focal point in vector‐borne disease ecology. However, efforts to generalize preliminary findings across studies and systems and translate these findings into disease control strategies are hindered by a lack of fundamental understanding of the processes shaping the vector microbiome and the interactions therein. Here, we use 16S rRNA sequencing and apply a community ecology framework to analyze microbiome community assembly and interactions in Ixodes pacificus, the Lyme disease vector in the western United States. We find that vertical transmission routes drive population‐level patterns in I. pacificus microbial diversity and composition, but that microbial function and overall abundance do not vary over time or between clutches. Further, we find that the I. pacificus microbiome is not strongly structured based on competition but assembles nonrandomly, potentially due to vector‐specific filtering processes which largely eliminate all but the dominant endosymbiont, Rickettsia. At the scale of the individual I. pacificus, we find support for a highly limited internal microbial community, and hypothesize that the tick endosymbiont may be the most important component of the vector microbiome in influencing pathogen dynamics.

Human T-lymphotropic virus type I and breastfeeding; systematic review and meta-analysis of the literature

Background: The human T-cell lymphotropic virus type-I (HTLV-I) is the first identified pathogenic human retrovirus. Breastfeeding has been reported to be the predominant route of vertical transmission of HTLV-I. The objective of this systematic review was to pool and evaluate the data on the transmission of HTLV-I with different infant-feeding practices on children born to HTLV-I-positive mothers. We conducted a systematic review of comparison of HTLV-I transmission risk to breastfed and bottle-fed babies. Methods: We searched the following databases: MEDLINE, SID, Magiran, and Cochrane Library. The search strategy was limited to articles in English. Initial screening identified 254 citations; of these, 96 potentially relevant articles were identified. After reviewing the 96 full-text articles in detail, 7 reports met the inclusion criteria for this review. Results: Pooled odds ratio (OR) and risk difference (RD) of HTLV-I transmission in the breastfed group compared to the bottle-fed infants were [OR = 3.48, 95% confidence interval (CI): 1.58-7.64, P = 0.0020, Cochran's Q = 27.7, P = 0.0010, and I2 = 67.5%] and (RD = 17.1%, 95% CI: 7.5%-26.7%, P < 0.0001, Cochran's Q = 106, P < 0.0001, and I2 = 91.5%). So, we have evidence to support that exclusive breast feeding more than 6 months in comparison to bottle feeding highly increases transmission rate of HTLV-I infection. We have also enough evidence to support that exclusive breast feeding up to 6 months compared to bottle feeding does not increase transmission rate of HTLV-I infection (pooled OR = 0.912, CI: 0.45-1.80; OR: 3.83, CI: 1.80-8.10, respectively). Conclusion: The current meta-analysis showed that short period (less than 6 months) of breastfeeding did not increase risk of HTLV-I infection transmission from mother to child among breastfeeders and more than 6 months of breastfeeding significantly increased the risk of HTLV-I infection. However, our meta-analysis shows that refraining from breastfeeding can decrease the risk of vertical HTLV-I transmission.

A systematic review and meta-analysis of vertical transmission route of HIV in Ethiopia

BackgroundThe burden of mother-to-child transmission rate of HIV is high and risk factors are common in Ethiopia. This systematic review and meta-analysis intended to provide the pooled estimation of mother-to-child transmission rate and its risk factors in Ethiopia.MethodsWe searched PubMed, Google Scholar, EMBASE and Web of Science electronic databases for all available references. We included observational studies including case-control, cohort, and cross-sectional studies. The search was further limited to studies conducted in Ethiopia and publish in English. Heterogeneity was checked using the I2 statistic. Egger’s test and the funnel plot were used to assess publication bias. A meta-analysis using a weighted inverse variance random-effects model was performed.ResultsA total of 18 studies with 6253 individuals were included in this systematic review and meta-analysis. Of these, 14 studies with 4624 individuals were used to estimate the prevalence. The estimated pooled prevalence of mother-to-child transmission of HIV was 11.4% (95% CI = 9.1–13.7). The pooled adjusted odds ratio (AOR) of mother-to-child transmission of HIV for the infants from rural area was 3.8 (95% CI = 1.4 to 6.3), infants delivered at home was 3.2 (95% CI = 1.2 to 5.2), infant didn’t take antiretroviral prophylaxis was 5.8 (95% CI = 1.5 to 10.3), mother didn’t take antiretroviral prophylaxis was 6.1 (95% CI = 2.5 to 9.6), mothers didn’t receive PMTCT intervention was 5.1 (95% CI = 1.6, 8.6), and on mixed feeding was 4.3 (95% CI = 1.8 to 6.7).ConclusionsThis systematic review and meta-analysis showed that mother-to-child transmission rate of HIV was high in Ethiopia. Being from the rural residence, home delivery, not taking antiretroviral prophylaxis, the absence of PMTCT intervention, and mixed infant feeding practices increased the risk of HIV transmission.Trial registrationIt is registered in the Prospero database: (PROSPERO 2017: CRD42017078232).

Numerical solution of nonlinear fractional SEIR epidemic model by using Haar wavelets

Throughout the world people have been suffering from the infectious diseases like Rubella, Herpes Simplex, Hepatitis B, Chagas, and HIV(AIDS) which have been causing loss of millions of lives and billions of rupees in cure. These diseases get transmitted via both horizontal and vertical transmission routes. One among the most recent mathematical models for modeling the above infectious diseases is fractional order nonlinear SEIR model [3] with non-constant population. In this paper, we have proposed a computationally faster and simpler numerical method based on Haar wavelets to solve the SEIR model. The error bounds have also been derived and validated.

A BIVALENT INACTIVATED VACCINE OF VIRAL NERVOUS NECROSIS VIRUS AND GROUPER IRIDOVIRUS APPLIED TO GROUPER BROODFISH (EPINEPHELUS COIOIDES) REDUCES THE RISK OF VERTICAL TRANSMISSION

Forty-one broodfish of orange-spotted groupers (Epinephelus coioides) were selected to evaluate the effectiveness of a viral nervous necrosis virus (VNNV) and grouper iridovirus (GIV) inactivated bivalent vaccine in grouper broodfish. Real-time quantitative PCR analysis showed that a detection rate of 10.5% (2/19) was found in egg specimens of VNNV and GIV, which carried approximately 1780 copies of GIV viral DNA in the egg specimens from broodfish before vaccination. This confirmed the vertical transmission route of GIV in broodfish. A significant increase of the anti-VNNV serum antibody titer was more than 50% in the high titer level (1:1810 to 1:5120) and 45% in the moderate titer level (1:452 to 1:1280), which were higher than those of the anti-GIV display, with 50% (10/20) in a titer of 1:57 to 1:320 and 40% (8/20) in a titer of 1:452 to 1:1280 one month after the vaccination. This result showed that the VNNV is a highly antigenic virus and can effectively induce neutralizing antibodies better than GIV. In addition, the VNNV and GIV viral copy numbers were 97.1 and 1780 copies per [Formula: see text]g host egg DNA from the broodfish before vaccination, respectively. One month after the vaccination, the viral genomes of VNNV and GIV were undetectable in egg specimens. The results show that immunization can induce the production of specific protective neutralizing antibodies, and the infective antigens can thereby be eliminated by the immunity. The results demonstrate that the specific antibodies of GIV and VNNV induced by vaccination can reduce the risk of vertical transmission of VNNV and GIV in grouper broodfish.

Maternal inheritance of bifidobacterial communities and bifidophages in infants through vertical transmission

BackgroundThe correct establishment of the human gut microbiota represents a crucial development that commences at birth. Different hypotheses propose that the infant gut microbiota is derived from, among other sources, the mother’s fecal/vaginal microbiota and human milk.ResultsThe composition of bifidobacterial communities of 25 mother-infant pairs was investigated based on an internal transcribed spacer (ITS) approach, combined with cultivation-mediated and genomic analyses. We identified bifidobacterial strains/communities that are shared between mothers and their corresponding newborns. Notably, genomic analyses together with growth profiling assays revealed that bifidobacterial strains that had been isolated from human milk are genetically adapted to utilize human milk glycans. In addition, we identified particular bacteriophages specific of bifidobacterial species that are common in the viromes of mother and corresponding child.ConclusionsThis study highlights the transmission of bifidobacterial communities from the mother to her child and implies human milk as a potential vehicle to facilitate this acquisition. Furthermore, these data represent the first example of maternal inheritance of bifidobacterial phages, also known as bifidophages in infants following a vertical transmission route.

Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles

Zika virus (ZIKV) is a mosquito-borne flavivirus that mostly causes asymptomatic infections or mild disease characterized by low-grade fever, rash, conjunctivitis, and malaise. However, the recent massive ZIKV epidemics in the Americas have also linked ZIKV infection to fetal malformations like microcephaly and Guillain-Barré syndrome in adults, and have uncovered previously unrecognized routes of vertical and sexual transmission. Here we describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug, which was more recently shown to inhibit multiple viruses. In cell culture-based assays, using reduction of cytopathic effect as read-out, suramin had an EC50 of ∼40 μM and a selectivity index of 48. In single replication cycle experiments, suramin treatment also caused a strong dose-dependent decrease in intracellular ZIKV RNA levels and a >3-log reduction in infectious progeny titers. Time-of-addition experiments revealed that suramin inhibits a very early step of the replication cycle as well as the release of infectious progeny. Only during the first 2 h of infection suramin treatment strongly reduced the fraction of cells that became infected with ZIKV, suggesting the drug affects virus binding/entry. Binding experiments at 4 °C using 35S-labeled ZIKV demonstrated that suramin interferes with attachment to host cells. When suramin treatment was initiated post-entry, viral RNA synthesis was unaffected, while both the release of genomes and the infectivity of ZIKV were reduced. This suggests the compound also affects virion biogenesis, possibly by interfering with glycosylation and the maturation of ZIKV during its traffic through the secretory pathway. The inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broad-spectrum activity warrant further evaluation of this compound as a potential therapeutic.