Elimination of a closed population of the yellow fever mosquito, Aedes aegypti, through releases of self-limiting male mosquitoes.

Establishment of novel mosquito control technologies such as the use of genetically engineered insects typically involves phased testing to generate robust data-sets that support its safe and effective use as a vector control tool. In this study, we demonstrate the ability of the transgenic self-limiting OX513A Aedes aegypti strain to suppress a wild type Ae. aegypti population in an outdoor containment facility in India.

Uncoating of common cold virus is preceded by RNA switching as determined by X-ray and cryo-EM analyses of the subviral A-particle.

During infection, viruses undergo conformational changes that lead to delivery of their genome into host cytosol. In human rhinovirus A2, this conversion is triggered by exposure to acid pH in the endosome. The first subviral intermediate, the A-particle, is expanded and has lost the internal viral protein 4 (VP4), but retains its RNA genome.

Characterization of rhinovirus subviral A particles via capillary electrophoresis, electron microscopy and gas-phase electrophoretic mobility molecular analysis: Part I.

During infection, enteroviruses, such as human rhinoviruses (HRVs), convert from the native, infective form with a sedimentation coefficient of 150S to empty subviral particles sedimenting at 80S (B particles). B particles lack viral capsid protein 4 (VP4) and the single-stranded RNA genome. On the way to this end stage, a metastable intermediate particle is observed in the cell early after infection.

Insights into minor group rhinovirus uncoating: the X-ray structure of the HRV2 empty capsid.

Upon attachment to their respective receptor, human rhinoviruses (HRVs) are internalized into the host cell via different pathways but undergo similar structural changes. This ultimately results in the delivery of the viral RNA into the cytoplasm for replication. To improve our understanding of the conformational modifications associated with the release of the viral genome, we have determined the X-ray structure at 3.

Liposomal nanocontainers as models for viral infection: monitoring viral genomic RNA transfer through lipid membranes.

After uptake into target cells, many nonenveloped viruses undergo conformational changes in the low-pH environment of the endocytic compartment. This results in exposure of amphipathic viral peptides and/or hydrophobic protein domains that are inserted into and either disrupt or perforate the vesicular membranes. The viral nucleic acids thereby gain access to the cytosol and initiate replication.

Entry of a heparan sulphate-binding HRV8 variant strictly depends on dynamin but not on clathrin, caveolin, and flotillin.

The major group human rhinovirus type 8 can enter cells via heparan sulphate. When internalized into ICAM-1 negative rhabdomyosarcoma (RD) cells, HRV8 accumulated in the cells but caused CPE only after 3 days when used at high MOI. Adaptation by three blind passages alternating between RD and HeLa cells resulted in variant HRV8v with decreased stability at acidic pH allowing for productive infection in the absence of ICAM-1.

Immunolocalization of Picornavirus RNA in infected cells with antibodies to Tyr-pUp, the covalent linkage unit between VPg and RNA.

The genomic RNA of picornaviruses is attached to a small protein (VPg) via a covalent bond between a tyrosine and a 5'-terminal uridine phosphate. The same structure is present in potyvirus and calicivirus families. VPgs play a key role in initiation of viral replication by acting as primers for RNA synthesis.

Liposomal leakage induced by virus-derived peptides, viral proteins, and entire virions: rapid analysis by chip electrophoresis.

Permeabilization of model lipid membranes by virus-derived peptides, viral proteins, and entire virions of human rhinovirus was assessed by quantifying the release of a fluorescent dye from liposomes via a novel chip electrophoretic assay. Liposomal leakage readily occurred upon incubation with the pH-sensitive synthetic fusogenic peptide GALA and, less efficiently, with a 24mer peptide (P1-N) derived from the N-terminus of the capsid protein VP1 of human rhinovirus 2 (HRV2) at acidic pH. Negative stain transmission electron microscopy showed that liposomes incubated with the rhinovirus-derived peptide remained largely intact.

Human rhinovirus 14 enters rhabdomyosarcoma cells expressing icam-1 by a clathrin-, caveolin-, and flotillin-independent pathway.

Intercellular adhesion molecule 1 (ICAM-1) mediates binding and entry of major group human rhinoviruses (HRVs). Whereas the entry pathway of minor group HRVs has been studied in detail and is comparatively well understood, the pathway taken by major group HRVs is largely unknown. Use of immunofluorescence microscopy, colocalization with specific endocytic markers, dominant negative mutants, and pharmacological inhibitors allowed us to demonstrate that the major group virus HRV14 enters rhabdomyosarcoma cells transfected to express human ICAM-1 in a clathrin-, caveolin-, and flotillin-independent manner.

Chip electrophoretic characterization of liposomes with biological lipid composition: Coming closer to a model for viral infection.

In first attempts at elucidating the transfer of the RNA genome of a human Rhinovirus through lipid membranes in vitro we made use of liposomes decorated with recombinant receptors. This model system was characterized previously by CE but suffered from the requirement for inclusion of polyethylene glycol-modified lipids for reliable separations [Weiss, V. U.

Low pH-triggered beta-propeller switch of the low-density lipoprotein receptor assists rhinovirus infection.

Minor group human rhinoviruses (HRVs) bind three members of the low-density lipoprotein receptor (LDLR) family: LDLR proper, very-LDLR (VLDLR) and LDLR-related protein (LRP). Whereas ICAM-1, the receptor of major group HRVs actively contributes to viral uncoating, LDLRs are rather considered passive vehicles for cargo delivery to the low-pH environment of endosomes. Since the Tyr-Trp-Thr-Asp beta-propeller domain of LDLR has been shown to be involved in the dissociation of bound LDL via intramolecular competition at low pH, we studied whether it also plays a role in HRV infection.

Predictive bioinformatic identification of minor receptor group human rhinoviruses.

Major group HRVs bind intercellular adhesion molecule 1 and minor group HRVs bind members of the low-density lipoprotein receptor (LDLR) family for cell entry. Whereas the former share common sequence motives in their viral capsid proteins (VPs), in the latter only a lysine residue within the binding epitope in VP1 is conserved; this lysine is also present in "K-type" major group HRVs that fail to use LDLR for infection. By using the available sequences three-dimensional models of VP1 of all HRVs were built and binding energies, with respect to module 3 of the very-low-density lipoprotein receptor, were calculated.

Mimicking virus attachment to host cells employing liposomes: analysis by chip electrophoresis.

Electrophoresis on a chip increasingly replaces electrophoresis in the capillary format because of its speed and containment of the sample within a disposable cartridge. In this paper we demonstrate its utility in the analysis of the interaction between a virus and a liposome-anchored receptor, mimicking viral attachment to host cells. This became possible because detergents, obligatory constituents of the BGE for capillary electrophoretic separation of the virus, were not necessary in the chip format.