Leonardo C. Caserta

Serum Metabolic Alterations upon Zika Infection

Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membranes outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.

Hepatitis C virus: Promising discoveries and new treatments.

Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.

Coronaviruses Detected in Brazilian Wild Birds Reveal Close Evolutionary Relationships with Beta- and Deltacoronaviruses Isolated From Mammals

This study showed that the most of the coronaviruses (CoVs) detected in Brazilian wild birds clustered with the mouse hepatitis virus A59 strain, belonging to the BetaCoV group. Furthermore, CoV detected in two different bird species, Amazona vinacea and Brotogeris tirica, clustered with a CoV isolated from Sparrow (SpaCoV HKU17) belonging to a monophyletic group related with the CoVs isolated from swines (PorCoV HKU15), both belonging to the DeltaCoV genus, previously unreported in South America. Considering the risk of inter-species host switching and further adaptation to new hosts, detection in bird species of CoVs closely related to mammal CoVs should warn for the potential emergence of new threatening viruses.

Phylogenetic and phylogeographic mapping of the avian coronavirus spike protein-encoding gene in wild and synanthropic birds.

Abstract The evolution and population dynamics of avian coronaviruses (AvCoVs) remain underexplored. In the present study, in-depth phylogenetic and Bayesian phylogeographic studies were conducted to investigate the evolutionary dynamics of AvCoVs detected in wild and synanthropic birds. A total of 500 samples, including tracheal and cloacal swabs collected from 312 wild birds belonging to 42 species, were analysed using molecular assays. A total of 65 samples (13%) from 22 bird species were positive for AvCoV. Molecular evolution analyses revealed that the sequences from samples collected in Brazil did not cluster with any of the AvCoV S1 gene sequences deposited in the GenBank database. Bayesian framework analysis estimated an AvCoV strain from Sweden (1999) as the most recent common ancestor of the AvCoVs detected in this study. Furthermore, the analysis inferred an increase in the AvCoV dynamic demographic population in different wild and synanthropic bird species, suggesting that birds may be potential new hosts responsible for spreading this virus.

Efficient detection of Zika virus RNA in patients’ blood from the 2016 outbreak in Campinas, Brazil

Infection with Zika virus (ZIKV), a mosquito-borne flavivirus has been casually linked with increased congenital microcephaly in Brazil from 2015 through 2016. Sensitive and specific diagnosis of patients with Zika fever (ZIKF) remains critical for patient management. We developed a ZIKV NS5 qRT-PCR assay by combining primers described by Balm et al. and a new Taqman probe. The assay was evaluated and compared with another assay described by Lanciotti et al. (ZIKV 1107) using 51 blood and 42 urine samples from 54 suspected ZIKV patients. ZIKV NS5 performed better in terms of sensitivity with more samples detected as ZIKV-positive (n = 37) than ZIKV 1107 (n = 34) for urine, and ZIKV-positive (n = 29) than ZIKV 1107 (n = 26) for blood. Both assays displayed good overall agreement for urine (κappa = 0.770) and blood (κappa = 0.825) samples. Improved availability of validated diagnostic tests, such ZIKV NS5 qRT-PCR, will be critical to ensure adequate and accurate ZIKV diagnosis.

Avian coronavirus isolated from a pigeon sample induced clinical disease, tracheal ciliostasis, and a high humoral response in day-old chicks

ABSTRACT The detection of avian coronaviruses (AvCoV) in wild birds and the emergence of new AvCoV have increased in the past few years. In the present study, the pathogenicity of three AvCoV isolates was investigated in day-old chicks. One AvCoV isolated from a pigeon, which clustered with the Massachusetts vaccine serotype, and two AvCoV isolated from chickens, which grouped with a Brazilian genotype lineage, were used. Clinical signs, gross lesions, histopathological changes, ciliary activity, viral RNA detection, and serology were evaluated during 42 days post infection. All AvCoV isolates induced clinical signs, gross lesions in the trachea, moderate histopathological changes in the respiratory tract, and mild changes in other tissues. AvCoV isolated from the pigeon sample caused complete tracheal ciliostasis over a longer time span. Specific viral RNA was detected in all tissues, but the highest RNA loads were detected in the digestive tract (cloacal swabs and ileum). The highest antibody levels were also detected in the group infected with an isolate from the pigeon. These results confirm the pathogenicity of Brazilian variants, which can cause disease and induce gross lesions and histopathological changes in chickens. Our results suggest that non-Galliformes birds can also play a role in the ecology of AvCoV.