Expression of biologically active envelope glycoprotein from the acutely pathogenic simian immunodeficiency virus SIVsmmPBj

The full-length envelope (env) gene from the most acutely pathogenic primate lentivirus described so far, the simian immunodeficiency virus SIVsmmPBj14 was expressed by a recombinant vaccinia virus vector (vv-env4) and was completely characterized as a previous step for its use as an immunogen in vaccination trials. Radioimmunoprecipitation and Western blot experiments indicated that SIVsmmPBj gp160 precursor was processed into gp120 and gp41 subunits, and that gp120 was released into the medium. Flow cytometry analysis showed that recombinant SIVsmmPBj was transported to and expressed on the surface of vvenv4-infected cells. Biochemical analysis of virus-like particles produced by coinfection of cells with recombinant vaccinia viruses expressing SIVsmmPBj Env (vv-env4) and Gag (vv-wtgag) proteins revealed that the Env glycoprotein was incorporated into core-like particles. Furthermore, cells expressing SIVsmmPBjenv gene products were found to undergo fusion with the same CD4+ cell lines in which the whole provirus has been shown to form syncytia. © 1994 Kluwer Academic Publishers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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