Mosquito-borne viruses, including dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV), pose major threats to public health in tropical and subtropical regions worldwide. Neonates are particularly vulnerable, and the associated disease burden has drawn increasing attention. Routes of neonatal infection include vertical mother-to-child transmission (transplacental and peripartum) and postnatal mosquito bites. Clinical manifestations are often nonspecific; a proportion of cases may progress to central nervous system infection, hemorrhagic disease, or long-term neurodevelopmental impairment, with serious consequences for survival and quality of life. Although China has issued prevention and control guidelines for adults and pregnant women, systematic clinical guidance tailored to neonates remains lacking. In response, the Perinatal Group of the Pediatric Branch of the Chinese Medical Doctor Association convened a multidisciplinary panel to develop this expert consensus, integrating the latest international evidence with China's practical prevention and control experience. The consensus addresses epidemiology; the effects of maternal infection on fetuses and neonates; clinical manifestations; diagnosis and differential diagnosis; early warning indicators of severe disease; therapeutic strategies and supportive care; and prevention and maternal-infant management. It aims to provide evidence-based, standardized, and practical guidance for frontline clinicians managing neonatal mosquito-borne viral infections.
Humans ; Zika Virus Infection/therapy* ; Infant, Newborn ; Chikungunya Fever/therapy* ; Dengue/prevention & control* ; Female ; Pregnancy ; Consensus

The effects of host factors ADP-ribosylation factor 4 (ARF4) and ADP-ribosylation factor 5 (ARF5) upon Zika virus (ZIKV) infection in vivo were characterized by construction of gene knockout mice via CRISPR-Cas9. Firstly, ARF5 and ARF4 genes were modified by the CRISPR-Cas9 system and then microinjected into the fertilized eggs of C57BL/6JGpt mice. Fertilized eggs were transplanted to obtain ARF4 or ARF5 knockout (ARF4KO or ARF5KO) mice, and ARF4/5 double knockout mice were achieved by the mating between ARF4KO and ARF5KO mice (ARF4KO/ARF5KO). Then, the mouse genotypes were identified by PCR to identify the positive knockout mice, and RT-qPCR was employed to examine the knockout efficiency. The mice were then infected with ZIKV and the blood and tissue samples were collected after 2, 4, and 6 days. RT-qPCR was then employed to determine the virus load, and hematoxylin-eosin staining was employed to observe the pathological changes in the tissue. The results showed that expected PCR bands were detected from ARF4KO^-/+, ARF5KO^-/-, and ARF4KO^-/+/ARF5KO^-/- mice, respectively. The results of mRNA transcription measurement indicated the significant knockdown of ARF4 by 37.8%-50.0% but not ARF5 in ARF4KO^-/+ compared with the wild-type mice. Meanwhile, complete knockout of ARF5 and no changes in ARF4 were observed in ARF5KO^-/- mice. Additionally, completed knockout of ARF5 and down-regulated mRNA level of ARF4 in the lung, kidney, and testis were detected in ARF4KO^-/+/ARF5KO^-/-mice in comparison with the wild-type mice. The virus load in the serum decreased in ARF4KO^-/+ mice, while it showed no significant change in ARF5KO^-/- or ARF4KO^-/+/ARF5KO^-/- mice compared with that in the wild type. Meanwhile, ARF4KO^-/+ mice showcased no significant difference in virus load in various tissues but attenuated pathological changes in the brain and testis compared with the wild-type mice. We successfully constructed ARF4KO and ARF5KO mice by CRISPR-Cas9 in this study. ARF4 rather than ARF5 is essential for ZIKV infection in vivo. This study provided animal models for studying the roles of ARF4 and ARF5 in ZIKV infection and developing antivirals.
Animals ; ADP-Ribosylation Factors/metabolism* ; Zika Virus Infection/genetics* ; Mice ; Mice, Knockout ; Zika Virus/genetics* ; Mice, Inbred C57BL ; CRISPR-Cas Systems ; Viral Load ; Male ; Female

Flavivirus ; Humans ; Immunity ; Vaccines ; Zika Virus ; Zika Virus Infection/prevention & control*

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.
Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; Humans ; Prospective Studies ; SARS-CoV-2 ; Vasoactive Intestinal Peptide/therapeutic use* ; Zika Virus ; Zika Virus Infection/drug therapy*

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*

OBJECTIVES: To estimate the number and risk of imported infections resulting from people visiting Asian and Latin American countries.METHODS: The dataset of visitors to 5 Asian countries with dengue were analyzed for 2016 and 2017, and in the Philippines, Thailand and Vietnam, imported cases of zika virus infection were also reported. For zika virus, a single imported case was reported from Brazil in 2016, and 2 imported cases reported from the Maldives in 2017. To understand the transmissibility in 5 Southeast Asian countries, the estimate of the force of infection, i.e., the hazard of infection per year and the average duration of travel has been extracted. Outbound travel numbers were retrieved from the World Tourism Organization, including business travelers.RESULTS: The incidence of imported dengue in 2016 was estimated at 7.46, 15.00, 2.14, 4.73 and 2.40 per 100,000 travelers visiting Philippines, Indonesia, Thailand, Malaysia and Vietnam, respectively. Similarly, 2.55, 1.65, 1.53, 1.86 and 1.70 per 100,000 travelers in 2017, respectively. It was estimated that there were 60.1 infections (range: from 16.8 to 150.7 infections) with zika virus in Brazil, 2016, and 345.6 infections (range: from 85.4 to 425.5 infections) with zika virus in the Maldives, 2017.CONCLUSION: This study emphasizes that dengue and zika virus infections are mild in their nature, and a substantial number of infections may go undetected. An appropriate risk assessment of zika virus infection must use the estimated total size of infections.
Asia, Southeastern ; Asian Continental Ancestry Group ; Brazil ; Commerce ; Dataset ; Dengue ; Humans ; Incidence ; Indian Ocean Islands ; Indonesia ; Korea ; Latin America ; Malaysia ; Philippines ; Risk Assessment ; Thailand ; Vietnam ; Zika Virus ; Zika Virus Infection

OBJECTIVE: To establish a non-coated enzyme-linked immunosorbent assay (ELISA) based on zika virus envelope (E) protein for detecting the expression of E protein in infected cells. METHODS: Adherent Vero-143 cells infected with zika virus in a 96-well plate were fixed, and the antibodies against zika virus E protein were added at an optimized concentration to establish the non-coated ELISA method for E protein. The antiviral activities of lignans compound C1 was evaluated using this method. The accuracy of this non-coated ELISA was verified by RT-PCR, and the cross reaction with dengue virus was assessed. RESULTS: After optimization, the background absorbance at 450 nm of uninfected cells was reduced to about 0.20. The antiviral activities of lignans compound C1 detected by this method were basically consistent with the results of RT-PCR. No cross reaction with dengue virus was found in this assay. CONCLUSIONS A non- coated ELISA method based on zika virus E protein was established, which can be used for screening antiviral agents against zika virus.
Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Viral Envelope Proteins ; Zika Virus ; Zika Virus Infection

Zika virus infection is, typically, either asymptomatic or causes mild illness; however, it may present severe clinical manifestations in neonates. Zika virus can be transmitted from a pregnant woman to her fetus, subsequently causing microcephaly and serious brain anomalies. Recently, the full spectrum of anomalies in neonates congenitally infected by Zika virus has been delineated as congenital Zika syndrome. Five major features are unique to congenital Zika syndrome: severe microcephaly with a partially collapsed skull, thin cerebral cortices with subcortical calcifications, macular scarring and focal pigment mottling of the retina, congenital contractures, and extrapyramidal symptoms. Recognition of this phenotype in neonates and infants by clinicians can help ensure appropriate etiologic evaluation of Zika virus infection and determine the required duration of follow-up and clinical care. Neonates with congenital Zika virus infection should be evaluated by a team of multiple specialists within the first year of life; the evaluations should include assessments of vision, hearing, feeding, growth, and neurodevelopmental function. Moreover, it is recommended that infants who show laboratory evidence of congenital Zika virus infection without apparent abnormalities be continuously monitored and screened by the primary care provider; repeated hearing tests should be carried out for such infants.
Brain ; Cerebral Cortex ; Cicatrix ; Contracture ; Culicidae ; Female ; Fetus ; Follow-Up Studies ; Hearing ; Hearing Tests ; Humans ; Infant ; Infant, Newborn* ; Microcephaly ; Phenotype ; Pregnant Women ; Primary Health Care ; Retina ; Skull ; Specialization ; Zika Virus Infection* ; Zika Virus*

The recent epidemic of Zika virus in South America caused people around the world to exhibit an increased interest in the impact of arboviral illnesses. In Korea, malaria and Japanese encephalitis are the most important mosquito-borne diseases that occur indigenously. However, with the continuously increasing number of international travelers, the incidence of imported arboviral illnesses is also increasing. Currently, dengue fever is the most common mosquito-borne disease among Korean international travelers. The number of patients with Japanese encephalitis, chikungunya fever, and Zika virus infection is also on the rise. Many countries that have disease-transmitting mosquitoes have already experienced autochthonous arboviral infections due to the introduction of viruses by travelers. Moreover, with global warming and urbanization of the areas in which mosquito-borne diseases occur, the environment is becoming more favorable for mosquito-borne diseases. This concise review describes the current status and outlook of mosquito-borne diseases in Korea.
Chikungunya Fever ; Culicidae ; Dengue ; Encephalitis, Japanese ; Global Warming ; Humans ; Incidence ; Korea* ; Malaria ; South America ; Urbanization ; Zika Virus ; Zika Virus Infection

Antimicrobial resistance and emerging infectious diseases, including avian influenza, Ebola virus disease, and Zika virus disease have significantly affected humankind in recent years. In the premodern era, no distinction was made between animal and human medicine. However, as medical science developed, the gap between human and animal science grew deeper. Cooperation among human, animal, and environmental sciences to combat emerging public health threats has become an important issue under the One Health Initiative. Herein, we presented the history of One Health, reviewed current public health threats, and suggested opportunities for the field of public health through better understanding of the One Health paradigm.
Animals ; Communicable Diseases ; Communicable Diseases, Emerging ; Drug Resistance, Microbial ; Ecology ; Hemorrhagic Fever, Ebola ; Humans ; Influenza in Birds ; Korea ; Public Health* ; Zika Virus Infection ; Zoonoses