JAK/STAT-deficient cell lines

Mutant cell lines B3 and B10, which are unresponsive to both interferon (IFN)-alpha and IFN-gamma, and line B9, which does not respond to IFN-gamma stimulation, are described. The mutants were submitted to fluorescence-activated cell sorting (FACS) from a cellular pool, which was obtained from the parental cell line 2C4 after several rounds of mutagenesis. The unresponsiveness to IFN stimulation was observed both in terms of expression of cell surface markers (CD2, class I and II HLAs) and mRNA expression of IFN-stimulated genes (2'-5' oligoadenylate synthetase (OAS), 9-27, and guanylate binding protein (GBP)). Genetic crossing of B3, B9 and B10 with U3 (STAT1-), gamma2a (JAK2-) and U4 (JAK1-) mutants, respectively, did not restore IFN responsiveness to the hybrid cell lines. However, when these cell lines were crossed with the same mutants, but using the pairwise crosses B3 x U4, B9 x U3 and B10 x U3, the cell hybrids recovered full IFN responsiveness. The present genetic experiments permitted us to assign the mutant cell lines B3, B9 and B10 to the U3, gamma2 and U4 complementation groups, respectively. These conclusions were supported by the analysis of IFN-stimulated genes in the mutants

First fatal case of CNS infection caused by Enterovirus A in Brazil

We describe what is to our knowledge the first fatal case of central nervous system Enterovirus infection in Brazil. Molecular and phylogenetic characterization revealed that Enterovirus A was the aetiologic agent of this case

Viral pathogenesis, modulation of immune receptor signaling and treatment.

During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that target immune receptor transmembrane signaling. Uncovering the exact molecular mechanisms underlying these critical points in viral pathogenesis will not only help us understand strategies used by viruses to escape from the host immune surveillance but also reveal new therapeutic targets for antiviral as well as immunomodulatory therapy. In this chapter, based on our current understanding of transmembrane signal transduction mediated by multichain immune recognition receptors (MIRRs) and the results of sequence analysis, we discuss the MIRR-targetingviral strategies of immune evasion and suggest their possible mechanisms that, in turn, reveal new points of antiviral intervention. We also show how two unrelated enveloped viruses, human immunodeficiency virus and human cytomegalovirus, use a similar mechanism to modulate the host immune response mediated by two functionally different MIRRs-T-cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly nonviral pathogens