Search Results (169)

The expanding distribution and geographic range of mosquitoes have potentially contributed to increased flaviviral dissemination and transmission. Despite the growing burden of flaviviral infections, there are no effective antiviral treatments or vaccines, highlighting the need for novel therapeutic targets. Tetraspanins, a superfamily of transmembrane domain glycoproteins involved in cellular organization, signaling, and protein–protein interactions have been recognized as potential mediators of flaviviral infection and transmission. While their roles in vertebrate hosts have been explored, their involvement in flaviviral replication and dissemination within medically important vectors remains poorly understood. In this study, we investigated the role of arthropod tetraspanins in mosquito cells and extracellular vesicles (EVs) derived from cells infected with Zika virus (ZIKV) and dengue virus (serotype 2; DENV2). Among several of the tetraspanins analyzed, only CD151 was significantly upregulated in both mosquito cells and in EVs derived from ZIKV/DENV2-infected cells. RNAi-mediated silencing of CD151 led to a marked reduction in viral burden, suggesting its crucial role in flavivirus replication. Inhibition of EV biogenesis using GW4869 further demonstrated that EV-mediated viral transmission contributes to flavivirus propagation. Additionally, co-immunoprecipitation and immunofluorescence analyses revealed direct interactions between CD151 and ZIKV NS2B and DENV2 capsid proteins. Overall, our findings highlight the functional importance of mosquito CD151 in the replication and transmission of ZIKV and DENV2. This study provides new insights into the molecular mechanisms of flaviviral infection in mosquitoes and suggests that targeting vector tetraspanins may offer a potential approach to controlling mosquito-borne flaviviruses. Full article

Orthoflaviviruses (formerly flaviviruses) are known for their role in numerous diseases affecting both humans and animals. Despite the worldwide distribution of orthoflaviviruses, individual species are only found in endemic or epidemic regions. However, in recent decades, certain orthoflaviviruses have spread beyond their traditional geographic boundaries, even crossing continents. Given the long-distance movements of birds, the knowledge of zoonotic orthoflaviviruses associated with birds is essential because of their possible introduction into new regions, as was the case with West Nile virus and Usutu virus. A thorough literature review was conducted on zoonotic orthoflaviviruses related to birds, including lesser-known (re-)emerging and neglected orthoflaviviruses that are limited to specific regions and/or avian hosts but have the potential to spread to a wider geographical area and pose a higher risk of transmission to humans. Several of these viruses possess significant zoonotic potential and can cause a wide spectrum of diseases in humans, ranging from mild febrile illnesses (Zika virus) to severe neuroinvasive diseases (tick-borne encephalitis, West Nile, Japanese encephalitis virus) and hemorrhagic fevers (yellow fever, dengue virus). Geographic distribution, hosts, vectors, incidence of human infections, and impact on human and animal health of zoonotic flaviviruses related to birds are critically reviewed. The viruses have been categorized based on the role of birds as an orthoflavivirus host and the clinical presentation in human infections. Full article

Mosquitoes of the Aedes and Culex genera are primary vectors of arboviruses such as the dengue, Zika, chikungunya (CHIKV), Oropouche, and West Nile viruses, causing millions of infections annually. Standard virus detection in mosquitoes requires capturing, transporting, and processing samples with a cold chain to preserve RNA, which is challenging in resource-limited areas. FTA cards preserve viral RNA at room temperature and have been used to collect mosquito saliva, a key sample for assessing transmission. However, most FTA-based traps require electricity or CO₂, limiting use in low-resource settings. This study adapted and evaluated the BR-ArboTrap, a low-cost trap derived from an oviposition trap, integrating a sugar-based attractant with FTA cards to collect mosquito saliva, without electricity or refrigeration. Aedes aegypti exposed to CHIKV were used in three experiments to evaluate: (i) RNA preservation under different conditions, (ii) the minimum number of positive mosquitoes for detection, and (iii) RNA amounts on FTA versus blood. RT-qPCR detected CHIKV RNA in 90% of FTA cards and 96% of exposed mosquitoes. RNA remained stable under varying conditions, with no significant difference compared to blood. BR-ArboTrap is an effective, affordable, and field-ready tool to enhance arbovirus surveillance in remote and low-resource areas. Full article

Several viruses have demonstrated the potential for infecting the human male genital tract, leading to potential host pathologic consequences and sexual transmission. Despite the testes being an immune-privileged niche of the body, viruses like Zika, mumps, Ebola, Marburg, and human immunodeficiency virus infect the lumen of testes. The human blood–testis barrier (BTB) is a specialized epithelial barrier responsible for protecting the developing sperm in the lumen of the seminiferous tubules from foreign antigen; however, testicular-tropic viruses possess the unique ability to modulate this barrier prior to entry into the lumen. Previous scientific reports identified immunomodulatory and viral-induced changes to BTB physiology during infection—a necessary step prior to viral entry into the testicular lumen. This review aims to explore the specific mechanisms employed by viruses to disrupt the human BTB and establish testicular infection. Full article

Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, which has high morbidity but low mortality rates in humans. The disease manifests in humans as high fever, headache, myalgia, arthralgia, photophobia, and, in some cases, meningitis and encephalitis. Additionally, a recent report suggests that OROV may cause fetal death, miscarriage, and microcephaly in newborns when women are infected during pregnancy, similar to the issues caused by the Zika virus (ZIKV), another mosquito-borne disease in the same regions. OROV was first reported in the mid-20th century in the Amazon basin. Since then, over 30 epidemics and more than 500,000 infection cases have been reported. The actual case numbers may be much higher due to frequent misdiagnosis, as OROV infection presents similar clinical symptoms to other co-circulating viruses, such as dengue virus (DENV), chikungunya virus (CHIKV), ZIKV, and West Nile virus (WNV). Due to climate change, increased travel, and urbanization, OROV infections have occurred at an increasing pace and have spread to new regions, with the potential to reach North America. According to the World Health Organization (WHO), over 10,000 cases were reported in 2024, including in areas where it was not previously detected. There is an urgent need to develop vaccines, antivirals, and specific diagnostic tools for OROV diseases. However, little is known about this surging virus, and no specific treatments or vaccines are available. In this article, we review the most recent progress in understanding virology, transmission, pathogenesis, diagnosis, host–vector dynamics, and antiviral vaccine development for OROV, and provide implications for future research directions. Full article

Oropouche fever is caused by the Oropouche virus (OROV; Bunyaviridae, Orthobunyavirus), one of the most frequent arboviruses that infect humans in the Brazilian Amazon. This year, an OROV outbreak was identified in Brazil, and its vertical transmission was reported, which was associated with fetal death and microcephaly. We describe the clinical manifestations identified in three cases of congenital OROV infection with confirmed serology (OROV-IgM) in the mother-newborn binomial. One of the newborns died, and post-mortem molecular analysis using real-time RT-qPCR identified the OROV genome in several tissues. All three newborns were born in the Amazon region in Brazil, and the mothers reported fever, rash, headache, myalgia, and/or retro-orbital pain during pregnancy. The newborns presented with severe microcephaly secondary to brain damage and arthrogryposis, suggestive of an embryo/fetal disruptive process at birth. Brain and spinal images identified overlapping sutures, cerebral atrophy, brain cysts, thinning of the spinal cord, corpus callosum, and posterior fossa abnormalities. Fundoscopic findings included macular chorioretinal scars, focal pigment mottling, and vascular attenuation. The clinical presentation of vertical OROV infection resembled congenital Zika syndrome to some extent but presents some distinctive features on brain imaging and in several aspects of its neurological presentation. A recognizable syndrome with severe brain damage, neurological alterations, arthrogryposis, and fundoscopic abnormalities can be associated with in utero OROV infection. Full article

One major challenge in preventing infectious diseases comes from human control behaviors. In the context of vector-borne diseases (VBDs), I explored how the waxing and waning of a human psychological emotion—fear—can generate diverse control actions, which, in turn, influence disease dynamics. Fear may diminish over time after being triggered but can also be reinforced when new triggers emerge. By integrating fear dynamics into a generic Ross–MacDonald model tailored for the Zika virus, I found that an increase in initial fear can enhance control efforts, thereby reducing the number of infected individuals and deaths. Once initial fear becomes strong enough to deplete the mosquito population, any further increase in fear no longer impacts disease dynamics. When initial fear is at an intermediate level, the increase in disease caused by greater decay in fear can be counterbalanced by increasing the frequency of fear triggers. Interestingly, when the control period is short and initial fear is at an intermediate level, increasing the frequency of fear reinforcement can lead to a “hydra effect”, which increases disease transmission. These findings help explain variations in human control efforts and provide insights for developing more effective disease control strategies that account for the fear dynamics of local communities. This work also contributes to advancing the theory at the intersection of human behavior, disease ecology, and epidemiology. Full article

Zika virus (ZIKV) is a mosquito-borne flavivirus of the family Flaviviridae. The association between ZIKV and microcephaly was first described in Brazil in 2015. The risk of vertical transmission occurs in pregnant women with or without symptoms, and the risk of malformation appears to be worse when infection occurs in the first and second trimesters of pregnancy. The rate of vertical transmission varies from 26 to 65%, and not all fetuses develop malformations. The incidence of malformations resulting from transmission is uncertain, ranging from 6–8% in the US to 40% in Brazil. Congenital ZIKV syndrome is a set of clinical manifestations that can affect the fetus of a mother infected with ZIKV. The manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular changes, congenital contractures, early hypertension, and pyramidal and extrapyramidal signs. Other findings such as growth restriction and fetal miscarriage/death may also occur. Our aim in this article is to review the literature on mosquito transmission, clinical presentation, serologic diagnosis, intrauterine transmission, pre- and postnatal imaging diagnostic findings, and short- and long-term follow-up. Full article

ZIKA fever (ZIKAF) is an emerging mosquito-borne flavivirus illness in humans. Regarding the etiological agent, ZIKA virus (ZIKAV), though it is known to be distributed in the tropics, causing sporadic cases, its rapid global expansion with pandemic potential has raised global concern. Due to its abrupt emergence in South American countries, the Caribbean, and the Americas, the WHO declared ZIKA a public health emergency of international concern in 2016. ZIKAV usually causes mild infections; however, its recent unusual presentations of Guillen–Barré syndrome in adults and microcephaly in newborn babies of ZIKAV-infected mothers in Brazil has caused concern among global public health authorities. Certain mutations on virus genomes have been found to be correlated with clinical severity, and its unusual transmission routes through sexual and blood transfusions emphasize the necessity for understanding its virological determinants and impact. Its abrupt re-emergence in India (2018–2019), particularly in Gujarat (2016), Tamil Nadu (2017), Uttar Pradesh (2021), Maharashtra, Kerala (2021), and Karnataka (2023), has indicated the need for urgent measures to strengthen surveillance systems and design effective prevention and control measures in this country. Given the global concern around ZIKAV, here, we reviewed current knowledge about global ZIKAV genetic lineages vis à vis the situation in India and discussed future priorities for ZIKAV research in India for effectively designing control strategies. Full article

Ilhéus Virus (ILHV) was first detected in 1944 in Ilhéus, state of Bahia, northeast Brazil. During cellular infection, orthoflaviviruses induce cellular changes related both to the replication process, the formation of replication complexes, and to structures resulting from cellular damage. Although more detailed data are available in the literature for other orthoflaviviruses, the relationship between ILHV, the formation of these structures, its replication cycle, and cellular changes remains unknown. One of the main objectives of this study is to characterize the primary ultrastructural changes in green monkey kidney epithelial cell lineage (Vero cell) infected with ILHV, as well as to map its replication cycle, virion structure, and genome. To achieve these objectives, Vero cell monolayers were infected with an MOI of 0.01 and collected at different times post-infection. Cell monolayers were evaluated under bright-field microscopy and transmission electron microscopy. Ultrastructural analyses confirmed that ILHV can induce the formation of double-membrane vesicles, convoluted membranes, and vesicular packets. These structures, like those observed in zika (ZIKV) and dengue (DENV) viruses, form replication complexes that aid ILHV’s replication process in cells. Our preliminary results reveal that ILHV infection induces cytopathogenesis like that observed in vitro studies for other arboviruses. Full article

Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms. However, the virus has been found to be associated with a variety of congenital neural abnormalities, including microcephaly in children and Guillain–Barre syndrome in adults. The exact prediction of the potential of ZIKV transmission is still enigmatic and underlines the significance of routine detection of the virus in suspected areas. ZIKV transmission from mother to fetus (including fetal abnormalities), viral presence in immune-privileged areas, and sexual transmission demonstrate the challenges in understanding the factors governing viral persistence and pathogenesis. This review illustrates the transmission patterns, epidemiology, control strategies (through vaccines, antivirals, and vectors), oncolytic aspects, molecular insights into neuro-immunopathogenesis, and other neuropathies caused by ZIKV. Additionally, we summarize in vivo and in vitro models that could provide an important platform to study ZIKV pathogenesis and the underlying governing cellular and molecular mechanisms. Full article

The Zika virus, known for its potential to induce neurological conditions such as microcephaly when transmitted vertically from infected mothers to infants, has sparked widespread concerns globally. Motivated by this, we propose an optimal control problem for the prevention of vertical Zika transmission. The novelty of this study lies in its consideration of time-dependent control functions, namely, insecticide spraying and personal protective measures taken to safeguard pregnant women from infected mosquitoes. New results provide a way to minimize the number of infected pregnant women through the implementation of control strategies while simultaneously reducing both the associated costs of control measures and the mosquito population, resulting in a decline in microcephaly cases. Full article

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. Full article

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations. Full article

Temperature is a determining factor for the viral cycle. In this study, we investigate the effect of different temperatures on the cycles of two important arboviruses—Zika (ZIKV) and Chikungunya (CHIKV)—in Vero (mammalian) and C6/36 (mosquito) cells. We compare genome quantification to infectivity at 28 °C and 37 °C in both cell types. Virus–cell interaction was also examined by transmission electron microscopy, allowing the observation of phenomena such as virus-surfing and giant forms for CHIKV, as well as the the scarcity of ZIKV in C6/36 cells compared to its cycle in mammalian cells. Full article