Disease relevance of Alphavirus

• The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal beta barrels of domain II of the glycoprotein E are inserted into the cellular membrane [1].
• Intracellular alphavirus nucleocapsids express a binding site for the cytoplasmic domain of the viral E2 spike glycoprotein [2].
• Do fusion pathways mediated by alphavirus E1 and influenza virus hemagglutinin (HA) that exemplify classes II and I differ to reflect the difference in their initial conformations, or concur to reflect the similarity in the final conformations [3]?
• Packaging of intron-containing genes into retrovirus vectors by alphavirus vectors [4].
• The E1 protein of rubella virus shows no significant homology with alphavirus E1 envelope proteins [5].

High impact information on Alphavirus

• Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons [6].
• Here we show that intracellular, but not extracellular, PAI-2 protected cells from the rapid cytopathic effects of alphavirus infection [7].
• These findings indicate that alphaviruses can trigger a caspase-mediated inactivation of Bcl-2 in order to evade the death protection imposed by this survival factor [8].
• A tyrosine-based motif in the cytoplasmic domain of the alphavirus envelope protein is essential for budding [9].
• Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins [10].

Chemical compound and disease context of Alphavirus

• These findings suggest that in the capping of alphavirus mRNAs the guanine is methylated before linkage to the mRNA molecule [11].
• When HTLV-I-transformed and tax-expressing human T-cell lines were infected with this recombinant retrovirus (LNLTK alpha virus), they expressed high levels of HSV TK and exhibited increased sensitivity to acyclovir, a nucleoside analog that is converted to the toxic anabolite after phosphorylation by the HSV TK [12].
• Sphingolipid and cholesterol dependence of alphavirus membrane fusion. Lack of correlation with lipid raft formation in target liposomes [13].
• A statistically significant similarity has been detected between the sequences of these domains and those of the C-terminal serine protease domains of alphavirus capsid proteins [14].
• Adaptation of alphaviruses to heparan sulfate: interaction of Sindbis and Semliki forest viruses with liposomes containing lipid-conjugated heparin [15].

Biological context of Alphavirus

• Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes into membrane fusion mode [16].
• Contrary to this model, we show that three cell types highly overexpressing functional Bcl-2 displayed caspase-3 activation and underwent apoptosis in response to infection with alphaviruses Semliki Forest and Sindbis as efficiently as vector control counterparts [8].
• When mutations preventing nsP1 palmitoylation were introduced into the genomes of these two alphaviruses, the mutant viruses remained viable and replicated to high titers, although their growth was slightly delayed [17].
• This phenotype is contrary to what has been observed for infection in vertebrate cells with a presumably functional RNase L gene and more resembled alphavirus replication in Aedes mosquito cells, in which the activity of replication complexes making plus stands was also found to decay with inhibition of translation [18].
• Along the 422 amino acids of the Semliki Forest virus (SFV) E2 envelope glycoprotein, we identified 13 peptide cassettes (ranging in size from 15 to 25 amino acids and designated A through N) that contain hydrophilic sequences flanked by amino acid sequences conserved in the E2 envelopes of the alphavirus family [19].

Anatomical context of Alphavirus

• To test this hypothesis, we used the RNA alphavirus Sindbis to express three known cyclin dependent kinase inhibitors (CKIs), p16(ink4), p21(waf/cip), and p27(kip1), and dominant negative mutant forms of four known G1 cyclin dependent kinases (CDKs), Cdk2, Cdk3, Cdk4, and Cdk6, in primary cultured rat superior cervical ganglion sympathetic neurons [20].
• The nsP1 palmitoylation-defective alphaviruses produced normal plaques in several cell types, but failed to give rise to plaques in HeLa cells, although they induced normal apoptosis of these cells [17].
• Compared to alphaviruses, processing of RV glycoprotein moieties occurred relatively slowly and the transport of glycoproteins E2 and E1 to the plasma membrane was inefficient [21].
• Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon, Salmo salar L [22].
• It has been observed, however, that live, attenuated mutants of the alphavirus, Venezuelan equine encephalitis virus (VEE), induce protection from virulent challenge at the respiratory mucosa even after parenteral inoculation [23].

Gene context of Alphavirus

• Retinoblastoma protein purification and transduction of retina and retinoblastoma cells using improved alphavirus vectors [24].
• An arthrogenic alphavirus induces monocyte chemoattractant protein-1 and interleukin-8 [25].
• This turnover of replication complexes that were stable in cells containing RNase L suggested that RNase L plays some role, albeit possibly indirect, in the formation of stable replication complexes during alphavirus infection [18].
• DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses [26].
• LRP works as a receptor for alphaviruses and is associated with the metastatic potential of solid tumors where it was first identified [27].

Analytical, diagnostic and therapeutic context of Alphavirus

• On the basis of a cross-reactivity enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition assay, eight antigenic determinants (epitopes) on the E1 glycoprotein have been identified, ranging in reactivity from WEE-specific to alphavirus group reactive [28].

References