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Topical news snippets about viruses that affect people.  And other things. Like zombies B-)
Curated by Ed Rybicki
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A novel platform for virus-like particle-display of flaviviral envelope domain III: induction of Dengue and West Nile virus neutralizing antibodies

A novel platform for virus-like particle-display of flaviviral envelope domain III: induction of Dengue and West Nile virus neutralizing antibodies | Virology News | Scoop.it

CD16-RIgE is a chimeric human membrane glycoprotein consisting of the CD16 ectodomain fused to the transmembrane domain and cytoplasmic tail of the gamma chain of the high affinity receptor of IgE (RIgE). Coexpression of CD16-RIgE and HIV-1 Pr55Gag polyprotein precursor (Pr55GagHIV) in insect cells resulted in the incorporation of CD16-RIgE glycoprotein into the envelope of extracellular virus-like particles (VLPs), a phenomenon known as pseudotyping. Taking advantage of this property, we replaced the CD16 ectodomain of CD16-RIgE by the envelope glycoprotein domain III (DIII) of dengue virus serotype 1 (DENV1) or West Nile virus Kunjin (WNVKun). The two resulting chimeric proteins, DIII-DENV1-RIgE and DIII-WNVKun-RIgE, were addressed to the plasma membrane, exposed at the surface of human and insect cells, and incorporated into extracellular VLPs when coexpressed with Pr55GagHIV in insect cells. The DIII domains were accessible at the surface of retroviral VLPs, as shown by their reactivity with specific antibodies, and notably antibodies from patient sera. The DIII-RIgE proteins were found to be incorporated in VLPs made of SIV, MLV, or chimeric MLV-HIV Gag precursors, indicating that DIII-RIgE could pseudotype a wide variety of retroviral VLPs. VLP-displayed DIII were capable of inducing specific neutralizing antibodies against DENV and WNV in mice.


Although the neutralization response was modest, our data confirmed the capability of DIII to induce a flavivirus neutralization response, and suggested that our VLP-displayed CD16-RIgE-based platform could be developed as a vaccine vector against different flaviviruses and other viral pathogens.


HIV matrix illustration by Russell Kightley Media

Ed Rybicki's insight:

Love it: using retrovirus Gag polyproteins that bud out of insect cells to carry a chimaeric protein that elicits neutralising antibodies against dengue and West Nile viruses.  Love it because my lab has huge experience in making such particles, and we have tried to tout them as vehicles for display of other antigens...but haven't actually done it!

 

Modest titres, it must be noted: while I think this is a great paper, I am NOT convinced that retrovirus-derived VLPs will be of any use in such an application, because yields of particles via insect cells are simply too low.  Sad, but true.  HOWEVER: making a DNA vaccine out of it, on the other hand...would allow particles to be made in cells that receive the DNA, which would significantly increase their immunogenicity as it would expose cells that have NOT received DNA, to the immunogens.

 

Just a thought.

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The global distribution and burden of dengue

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes1. For some patients, dengue is a life-threatening illness2. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread3. The contemporary worldwide distribution of the risk of dengue virus infection4 and its public health burden are poorly known2, 5. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284–528) dengue infections per year, of which 96 million (67–136) manifest apparently (any level of clinical or subclinical severity).

Ed Rybicki's insight:

390 MILLION infections a year...!

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