The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell-Cell Communication: New Insights on Virus-Host Interactions.

The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus-host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus-host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome.

Host immunogenetics in tick-borne encephalitis virus infection-The CCR5 crossroad.

The human Tick-borne encephalitis virus (TBEV) infection is a complex event encompassing factors derived from the virus itself, the vectors, the final host, and the environment as well. Classically, genetic traits stand out among the human factors that modify the susceptibility and progression of infectious diseases. However, and although this is a changing scenario, studies evaluating the genetic factors that affect the susceptibility specifically to TBEV infection and TBEV-related diseases are still scarce. There are already some interesting pieces of evidence showing that some genes and polymorphisms have a real impact on TBEV infection. Also, the inflammatory processes involving tick-human interactions began to be understood in greater detail. This review focuses on the immunogenetic and inflammatory aspects concerning tick-host interactions, TBEV infections, and tick-borne encephalitis. Of note, it has been described that polymorphisms in CD209, GSTM1, IL-10, IL-28B, MMP9, OAS2, OAS3, and TLR3 have a statistically significant impact on TBEV infection. Besides, CCR5, its ligands, and the CCR5Δ32 genetic variant seem to have a very important influence on the infection and its immune responses. Taking this information into consideration, a special discussion regarding the effects of CCR5 on TBEV infection and tick-borne encephalitis will be presented. Emerging topics (such as exosomes, evasins, and CCR5 blockers) involving immunological and inflammatory aspects of TBEV-human interactions will also be addressed. Lastly, the current picture of TBEV infection and the importance to address the TBEV-associated problems through the One Health perspective will be discussed.

Tick-borne encephalitis carries a high risk of incomplete recovery in children.

OBJECTIVE: To examine long-term outcome after tick-borne encephalitis (TBE) in children. STUDY DESIGN: In this population-based cohort, 55 children with TBE with central nervous system involvement infected during 2004-2008 were evaluated 2-7 years later using the Rivermead post-concussion symptoms questionnaire (n = 42) and the Behavior Rating Inventory of Executive Functioning for parents and teachers (n = 32, n = 22, respectively). General cognitive ability was investigated in a subgroup (n = 20) using the Wechsler Intelligence Scale for Children, 4th edition. RESULTS: At long-term follow-up, two-thirds of the children experienced residual problems, the main complaints being cognitive problems, headache, fatigue, and irritability. More than one-third of the children were reported by parents or teachers to have problems with executive functioning on the Behavior Rating Inventory of Executive Functioning, mainly in areas involving initiating and organizing activities and working memory. Children who underwent Wechsler Intelligence Scale for Children, 4th edition testing had a significantly lower working memory index compared with reference norms. CONCLUSION: A large proportion of children experience an incomplete recovery after TBE with central nervous system involvement. Cognitive problems in areas of executive function and working memory are the most prevalent. Even if mortality and severe sequelae are low in children after TBE, all children should be followed after TBE to detect cognitive deficits.