It had been proposed that this mutant encoded an altered RNA guanylyltransferase enzyme with increased affinity for GTP, enabling it to replicate in cells with reduced levels of GTP

It had been proposed that this mutant encoded an altered RNA guanylyltransferase enzyme with increased affinity for GTP, enabling it to replicate in cells with reduced levels of GTP. Unger, T., Hilgenfeld, R., Bricogne, G., Neyts, J., La Colla, P., Puerstinger, G., Gonzalez, J.P., Leroy, E., Cambillau, C., Romette, J.L., Canard, B., 2008. The VIZIER project: preparedness against pathogenic RNA viruses. Antiviral Res. 78, 37C46]. This review highlights some of the major features of alphaviruses that have been investigated during recent years. After describing their classification, epidemiology and evolutionary history and the expanding Rabbit Polyclonal to PKNOX2 geographic distribution of Chikungunya computer virus, we review progress in understanding the structure and function of alphavirus replicative enzymes achieved under the VIZIER programme and the development of new disease control strategies. that together with the genus forms the family (Weaver et al., 2005). The alphaviruses are arthropod-borne (arboviruses), whereas the rubiviruses are transmitted via the respiratory tract. All arthropod-borne alphaviruses are antigenically related but most can be distinguished in cross-reactivity assessments (Chanas et al., 1976, Clarke and Casals, 1958, Karabatsos, 1975, Porterfield, 1961) with which they have been divided into 8 antigenic complexes: Eastern, Western, and Venezuelan equine encephalitis, Trocara (complex assigned based only on genetic divergence), Middelburg, Ndumu, Semliki Forest and Barmah Forest. In addition, you will find two non-arthropod-borne species, Salmon pancreatic disease computer virus and Southern elephant seal computer virus. Based on comparative sequence analysis, the BPH-715 arthropod-borne alphaviruses share a minimum of about 40% amino acid identity in the more divergent structural proteins BPH-715 and 60% in the non-structural proteins. 1.2. Structure, genome strategy and replication Alphavirus virions are approximately 70?nm in diameter. They are spherical with a lipid bilayer made up of heterodimeric protein spikes composed of two envelope glycoproteins E1 and E2. Many alphaviruses also contain a third envelope protein E3. The heterodimers are organized in a T?=?4 icosahedral lattice consisting of 80 trimers of E1CE2 complex. The enclosed nucleocapsid core consists of 240 copies of capsid protein and a single copy of the genomic BPH-715 RNA, although Aura computer virus is usually reported also to enclose the 26S subgenomic RNA (Rumenapf et al., 1995). The one-to-one relationship between glycoprotein heterodimers and nucleocapsid proteins is usually important BPH-715 in computer virus assembly. E1 is the fusion protein for computer virus entry into the acidic cytoplasmic endosomes. The structure of the E1 glycoprotein of Semliki Forest computer virus has been determined by crystallography (Lescar et al., 2001), revealing a fold closely related to the flavivirus envelope protein. The E2 glycoprotein extends outwards from your envelope and forms the petals of the spike that cover the underlying E1 protein fusion peptide at neutral pH (Mukhopadhyay et al., 2006). The four non-structural proteins are defined as nsP1, nsP2, nsP3 and nsP4. The genomic RNA is usually positive-stranded and serves as the mRNA for translation of the polyprotein precursor that is autocatalytically processed to the four non-structural viral BPH-715 proteins by the virus-encoded protease in nsP2 (Fig. 1 ). The non-structural proteins form the transcription/replication complex that mediates the synthesis of diverse viral RNAs of both polarities. The nsP1 protein was implicated in capping of viral RNAs (Ahola and K??ri?inen, 1995, Scheidel et al., 1989) and in initiation of negative-strand RNA synthesis (Sawicki and Sawicki, 1994). It is bound to the cytoplasmic membrane via a central amphipathic alpha helix located in the middle of the protein (Lampio et al., 2000). The nsP2 gene encodes a putative helicase domain name at the 5end and a protease domain name at the 3end, which presents a unique fold distantly related to that of known cysteine proteases (Russo et al., 2006). This.