MicrobiologyBytes

There is a pressing need for antiviral agents that are effective against multiple classes of viruses. Broad specificity might be achieved by targeting phospholipids that are widely expressed on infected host cells or viral envelopes. We reasoned that events occurring during virus replication (for example, cell activation or preapoptotic changes) would trigger the exposure of normally intracellular anionic phospholipids on the outer surface of virus-infected cells. A chimeric antibody, bavituximab, was used to identify and target the exposed anionic phospholipids. Infection of cells with Pichinde virus (a model for Lassa fever virus, a potential bioterrorism agent) led to the exposure of anionic phospholipids. Bavituximab treatment cured overt disease in guinea pigs lethally infected with Pichinde virus. Direct clearance of infectious virus from the blood and antibody-dependent cellular cytotoxicity of virus-infected cells seemed to be the major antiviral mechanisms. Combination therapy with bavituximab and ribavirin was more effective than either drug alone. Bavituximab also bound to cells infected with multiple other viruses and rescued mice with lethal mouse cytomegalovirus infections. Targeting exposed anionic phospholipids with bavituximab seems to be safe and effective. Our study demonstrates that anionic phospholipids on infected host cells and virions may provide a new target for the generation of antiviral agents.

Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. 2008 Nature Medicine 14: 1357-1362

Related:

• Unknown disease in South Africa identified as arenavirus infection

You may remember that the University of Leicester was named University of the Year 2008 in the Times Higher Education Awards, and that we’re all happy bunnies. The good news is that from 2010, you have not one but TWO choices to study microbiology at Leicester:

• Microbiology or:
• Medical Microbiology

Can you afford not to find out more?

Following on from the microscope basics video series, YouTube user lgines continues to produce the goods with a useful series of videos on aseptic technique:

Preparing a bacterial culture (broth to broth):

Preparing a bacterial culture (broth to plate):

Preparing a bacterial culture (slant to plate):

Preparing a smear from a broth culture:

Performing an isolation streak:

Gram staining:

Related:

• Microscope basics video series

YouTube is such a great teaching tool, and lgines has used it to share a very useful video series on how to use a microscope.

Part 1:

Part 2:

Part 3:

Recently I’ve been using YouTube to give class feedback on assignments as well as to post my thoughts about various areas of education and educational technology. How do you use YouTube in your teaching?

Related:

• YouTube Nature Channel
• YouTube BioMed Central Channel
• YouTube BMJ Channel

Dengue virus (DENV) is the most common arthropod-borne infection worldwide with 50–100 million cases annually. Despite its high clinical impact, little is known about the infectious cell entry pathway of the virus. Previous studies have shown conflicting evidence about whether the virus fuses directly with the cell plasma membrane or enters cells by receptor-mediated endocytosis.

Entry of DENV into hosts cells is mediated by the virus envelope glycoprotein E, which is organized in 90 homodimers on the surface of the virion. The E glycoprotein is involved in interaction with cellular receptors as well as the subsequent membrane fusion process. In vitro studies show that membrane fusion is triggered on exposure of the virus to low pH, when the E proteins undergo a dramatic re-organization which leads to the formation of trimers. The crystal structure of the E protein has been solved in its dimeric pre-fusion, and trimeric post-fusion configurations. Although much is known about the molecular mechanisms involved in the membrane fusion process, many critical questions regarding the cell entry pathway of flaviviruses remain unanswered.

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A recent paper dissects the cell entry pathway of DENV by tracking single fluorescently-labeled DENV particles in living cells expressing various fluorescent cellular markers, using real-time multi-color fluorescence microscopy (Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells. 2008 PLoS Pathog 4(12): e1000244). It shows that DENV particles are delivered to pre-existing clathrin-coated pits by diffusion along the cell surface. Following clathrin-mediated uptake, the majority of DENV particles are transported to early endosomes, which mature into late endosomes, where membrane fusion occurs. This is the first study that describes the cell entry process of DENV at the single particle level and therefore provides unique mechanistic and kinetic insights into the route of entry, endocytic trafficking behavior, and membrane fusion properties of individual DENV particles in living cells.

This work opens new avenues in flavivirus biology and will lead toward a better understanding of the critical determinants in DENV infection. Single-particle tracking has substantially enriched our knowledge of virus cell entry mechanisms and has revealed previously unknown aspects of virus-host interactions. The mechanistic and kinetic insights offered by this technique provide a better understanding of disease pathogenesis and may lead to a rational design of antiviral drugs and vaccines.

Related:

• First X-Ray Diffraction Image of a Single Virus Particle
• Imaging Poliovirus Entry in Live Cells
• How HIV Infects Cells – The Entry Claw
• Virus Entry
• Tracking Lyme Disease in Living Hosts

BBC NEWS

Humans could be protected from dengue fever by infecting the mosquitoes carrying it with a parasite which halves their lifespan. Australian scientists, writing in the journal Science, found that Wolbachia bacteria spread well through laboratory-bred mosquitoes. Only older mosquitoes pass on dengue – so killing them could cut disease. It remains to be seen how well the bacteria would spread outside the laboratory.

Related:

• Dengue Virus
• Wolbachia
• Clustering of dengue virus infections
• Malaria Researchers Identify New Mosquito Virus