Gut microbiota modulation induced by Zika virus infection in immunocompetent mice.

Gut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections.

Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV), Dengue, and Zika virus infections after treatment with oral antibiotics (Abx) that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8+ T cells associated with increased infection and immunopathology. Abx treatments that resulted in enhanced WNV susceptibility generated changes in the overall structure of the gut bacterial community and in the abundance of specific bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient to alter host immunity and WNV outcome. Our results identify oral Abx therapy as a potential environmental determinant of systemic viral disease, and they raise the possibility that perturbation of the gut microbiota may have deleterious consequences for subsequent flavivirus infections.

Zika virus infection modulates the bacterial diversity associated with Aedes aegypti as revealed by metagenomic analysis.

Zika is a re-emerging infection that has been considered a major threat to global public health. Currently at least 100 countries are at risk of Zika virus (ZIKV) transmission. Aedes aegypti is the main mosquito vector in the Americas. This vector is exposed to, and interacts symbiotically with a variety of microorganisms in its environment, which may result in the formation of a lifetime association. Here, the unknown effect that ZIKV exerts on the dynamic bacterial community harbored by this mosquito vector was investigated using a metagenomic analysis of its microbiota. Groups of Ae. aegypti were experimentally fed on sugar, blood and blood mixed with ZIKV, and held for 3 to 7 days after blood meal and eggs development respectively. The infected groups were processed by qPCR to confirm the presence of ZIKV. All groups were analyzed by metagenomics (Illumina Hiseq Sequencing) and 16S rRNA amplicon sequences were obtained to create bacterial taxonomic profiles. A core microbiota and exclusive bacterial taxa were identified that incorporate 50.5% of the predicted reads from the dataset, with 40 Gram-negative and 9 Gram-positive families. To address how ZIKV invasion may disturb the ecological balance of the Ae. aegypti microbiota, a CCA analysis coupled with an explanatory matrix was performed to support the biological interpretation of shifts in bacterial signatures. Two f-OTUs appeared as potential biomarkers of ZIKV infection: Rhodobacteraceae and Desulfuromonadaceae. Coincidentally, both f-OTUs were exclusively present in the ZIKV- infected blood-fed and ZIKV- infected gravid groups. In conclusion, this study shows that bacterial symbionts act as biomarkers of the insect physiological states and how they respond as a community when ZIKV invades Ae. aegypti. Basic knowledge of local haematophagous vectors and their associated microbiota is relevant when addressing transmission of vector-borne infectious diseases in their regional surroundings.

Initial experience with imported Zika virus infection in Spain / Experiencia inicial en infección importada por virus Zika en España

Introduction: A considerable increase of imported Zika virus (ZIKV) infection has been reported in Europe in the last year. This is the result of the large outbreak of the disease in the Americas, along with the increase in the numbers of travellers and immigrants arriving from ZIKV endemic areas. Methods: A descriptive study was conducted in the Tropical Medicine Unit of Hospital La Paz-Carlos III in Madrid on travellers returning from an endemic area for ZIKV from January to April 2016. Demographic, clinical and microbiological data were analyzed. Results: A total of 185 patients were screened for ZIKV (59.9% women, median age of 37.7±10.3 years). Main purpose of the travel was tourism to Colombia, Brazil, and México. Just under three-quarters (73%) were symptomatic, mostly with fever and headache. A total of 13 patients (7% of those screened) were diagnosed with ZIKV infections, of which four of them were pregnant. All of them were symptomatic patients, the majority immigrants, and mainly from Colombia. Diagnostic tests were based on positive neutralization antibodies (8 cases, 61.6%) and a positive RT-PCR in different organic fluids (7 cases, 53.8%) The four infected pregnant women underwent a neurosonography every 3 weeks, and no alterations were detected. RT-PCR in amniotic fluid was performed in three of them, with negative results. One of the children has already been born healthy. Conclusions: Our cases series represents the largest cohort of imported ZIKV to Spain described until now. Clinicians must increase awareness about the progression of the ZIKV outbreak and the affected areas so that they can include Zika virus infection in their differential diagnosis for travellers from those areas (AU)

Introducción: En el último año se ha registrado un importante aumento de casos de infección por virus Zika (ZIKV) importados en Europa. Este hecho es un reflejo de la epidemia que actualmente se está produciendo en las Américas, así como del aumento del número de viajeros e inmigrantes que proceden de zonas endémicas. Métodos: Estudio descriptivo de los viajeros retornados de área endémica para ZIKV en la Unidad de Medicina Tropical del Hospital La Paz-Carlos III en Madrid, de enero a abril de 2016. Se recogieron y analizaron datos demográficos, clínicos y microbiológicos. Resultados: Se cribaron para ZIKV un total de 185 pacientes (59,9% mujeres, mediana de edad de 37,7±10,3 años). El propósito por el que habían realizado el viaje fue por turismo a Colombia, Brasil y México. El 73% de los inicialmente cribados presentaron síntomas, fundamentalmente fiebre y cefalea. Se diagnosticó infección por ZIKV a 13 pacientes (7% de los cribados); 4 de ellos eran gestantes. Todos los casos con infección confirmada estaban sintomáticos, y la mayoría eran inmigrantes colombianos. El diagnóstico se basó en la presencia de anticuerpos neutralizantes positivos (8 casos, 61,6%) y RT-PCR positiva en diferentes fluidos orgánicos (7 casos, 53,8%). A las 4 gestantes infectadas se les realizó neurosonografía fetal seriada cada 3 semanas, no detectándose alteraciones en ninguna de ellas. En 3 casos se realizó RT-PCR en líquido amniótico, que fue negativo. Uno de los niños ha nacido, y está completamente sano. Conclusiones: Nuestra serie representa la cohorte más grande de infección por ZIKV importada en España hasta la fecha. Los clínicos deben estar alerta sobre la evolución de la epidemia del ZIKV y las zonas a las que afecta, para poder incluir la infección por ZIKV dentro del diagnóstico diferencial de viajeros que regresan de esas áreas (AU)

Persistence of Zika virus in semen 93 days after the onset of symptoms / Persistencia del virus Zika en semen 93 días tras el comienzo de los síntomas

Introduction: Zika virus is mainly transmitted through the bites of infected Aedes mosquitoes, although mother-to-child and sexual transmission have also been described. The presence of Zika virus in semen after infection seems to be not uncommon, but the duration of viral persistence has not been well-determined. Methods: Molecular, serological and cell culture methods were used for the diagnosis and follow up of a case of Zika virus infection imported from Venezuela. Serial samples of serum, urine and semen were analyzed to investigate the persistence of the Zika virus. Results: Zika virus was detected in semen samples up to 93 days after the onset of symptoms. Conclusions: Our results confirm the persistence of Zika virus in semen samples for long periods after infection (AU)

Introducción: El virus Zika se transmite fundamentalmente por la picadura de mosquitos Aedes infectados, aunque también es posible la transmisión de madre a hijo y la transmisión sexual. La presencia del virus Zika en semen tras la infección parece ser algo relativamente frecuente, pero la duración de la persistencia viral no es bien conocida. Métodos: Mediante técnicas moleculares, serológicas y cultivo celular se diagnosticó un caso de Zika importado de Venezuela y se tomaron muestra seriadas de suero, orina y semen para investigar la persistencia del virus. Resultados: El virus Zika fue detectado en muestras de semen recogidas 93días después del inicio de los síntomas. Conclusiones: Nuestros resultados confirman la persistencia del virus Zika en semen por períodos prolongados de tiempo después de la infección (AU)

Reply to the letter: Long term persistence of Zika virus after the onset of symptoms / Respuesta a la carta: Persistencia a largo plazo del virus Zika después de la aparición de los síntomas

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Mosquito control with green nanopesticides: towards the One Health approach? A review of non-target effects.

The rapid spread of highly aggressive arboviruses, parasites, and bacteria along with the development of resistance in the pathogens and parasites, as well as in their arthropod vectors, represents a huge challenge in modern parasitology and tropical medicine. Eco-friendly vector control programs are crucial to fight, besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as well as other arboviruses such as St. Louis encephalitis and Japanese encephalitis. However, research efforts on the control of mosquito vectors are experiencing a serious lack of eco-friendly and highly effective pesticides, as well as the limited success of most biocontrol tools currently applied. Most importantly, a cooperative interface between the two disciplines is still lacking. To face this challenge, we have reviewed a wide number of promising results in the field of green-fabricated pesticides tested against mosquito vectors, outlining several examples of synergy with classic biological control tools. The non-target effects of green-fabricated nanopesticides, including acute toxicity, genotoxicity, and impact on behavioral traits of mosquito predators, have been critically discussed. In the final section, we have identified several key challenges at the interface between "green" nanotechnology and classic biological control, which deserve further research attention.

Lipids and Pathogen Blocking by Wolbachia.

Mosquito-borne viruses are major human pathogens. Introducing Wolbachia into mosquitoes could reduce disease burdens because these bacteria block virus transmission. How Wolbachia does this is unclear, but new data show that modulation of host-cell lipids is critical.

Epidemiología y complicaciones neurológicas de la infección por el virus del Zika: un nuevo virus neurotropo emergente. Réplica / Epidemiology and neurological complications of infection by the Zika virus: a new emerging neurotropic virus. Reply

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Wolbachia Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes.

The recent association of Zika virus with cases of microcephaly has sparked a global health crisis and highlighted the need for mechanisms to combat the Zika vector, Aedes aegypti mosquitoes. Wolbachia pipientis, a bacterial endosymbiont of insect, has recently garnered attention as a mechanism for arbovirus control. Here we report that Aedes aegypti harboring Wolbachia are highly resistant to infection with two currently circulating Zika virus isolates from the recent Brazilian epidemic. Wolbachia-harboring mosquitoes displayed lower viral prevalence and intensity and decreased disseminated infection and, critically, did not carry infectious virus in the saliva, suggesting that viral transmission was blocked. Our data indicate that the use of Wolbachia-harboring mosquitoes could represent an effective mechanism to reduce Zika virus transmission and should be included as part of Zika control strategies.