Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Factors associated with thrombocytopenia in patients with dengue fever: a retrospective cohort study.

OBJECTIVE: Some patients with dengue fever tend to develop thrombocytopenia during the course of infection and are thus vulnerable to haemorrhagic manifestations and other complications. However, the factors associated with the development of thrombocytopenia are unknown. We aimed to identify factors associated with an increased risk of thrombocytopenia and haematological changes in patients with confirmed dengue fever. DESIGN: Retrospective cohort study. SETTING: Brazilian multicentre primary care databases. PARTICIPANTS: 387 patients had positive laboratory serological confirmation of dengue infection during 2014. The data were identified from two databases: Notification of Injury Information System (SINAN) and Municipal Laboratory. MAIN OUTCOME MEASURE: The presence of thrombocytopenia (platelet count <1 50×109/L). The associations of factors that predisposed patients to thrombocytopenia and haematological changes were analysed using logistic regression. ORs and 95% CIs were calculated. RESULTS: Among 387 patients, 156 had both dengue and thrombocytopenia. The risk factors associated with thrombocytopenia included male sex (OR: 1.77, 95% CI: 1.16 to 2.71, p=0.007), age of 46-64 years (OR: 2.20, 95% CI: 1.15 to 4.21, p=0.009) or ≥65 years (OR: 3.02, 95% CI: 1.40 to 6.50, p=0.002), presence of leucopenia (OR: 6.85, 95% CI: 4.27 to 10.99, p<0.001) and high mean corpuscular haemoglobin (MCH) levels (OR: 2.00, 95% CI: 1.29 to 3.12, p=0.005). CONCLUSION: Older age, male sex, presence of leucopenia and high MCH levels were identified as risk factors associated with the development of thrombocytopenia in this population.

Respiratory syncytial virus causes more hospitalizations and deaths in equatorial Brazil than influenza (including during the 2009 pandemic).

Despite numerous studies evaluating influenza and Respiratory Syncytial Virus (RSV), there is still a lack of knowledge about them, especially in tropical countries. We compared the relative importance of respiratory viruses by examining their spatiotemporal patterns, age-specific hospitalization data and mortality data for 2007-2012 obtained from official sources. The data were aggregated into "respiratory infection seasonal zones" formed combining states that had similar seasonal patterns of pneumonia and influenza (P&I). Equatorial-North where P&I peaks in the middle of the year, Equatorial-South where P&I peaks in the first semester and coincides with the rainy-season, Subtropical where P&I peaks are clearly concentrated in the winter season, and Tropical Midwest and South-East where P&I peaks are a transition between the South-Equatorial and the Sub-tropical. Our analyses indicate that RSV has higher impact than influenza in equatorial region of Brazil, which was particularly evident during the circulation of the 2009pdm strain, and suggests that seasonal influenza may have a lower impact in Equatorial Brazil (and perhaps in other tropical regions of the world) than previously considered. Accordingly, we suggest that the broad assumption that influenza is the main cause of viral respiratory hospitalizations and death in equatorial regions be questioned with greater emphasis in future studies.