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Re: biopharm post# 225223

Friday, 08/05/2016 10:35:05 PM

Friday, August 05, 2016 10:35:05 PM

Post# of 345788

Scripps Florida Scientist Awarded $2.3 Million to Study Dengue Fever and Related Viruses

JUPITER, FL – March 27, 2014 – The outbreak of dengue fever that infected some 20 people in Florida’s Martin County late last year unnerved many who feared the tropical disease had once again established a foothold in Florida. The last outbreaks occurred in 2009 and 2010 in Key West—before that, the disease hadn’t struck Florida in more than 70 years.

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded $2.3 million from the National Institutes of Health to study a category of viruses that cause dengue fever, West Nile, yellow fever and other diseases spread by mosquitoes and ticks. These diseases can result in flulike symptoms, extreme pain (dengue has been called “bone-break fever”) and, in some cases, encephalitis.

This family of viruses, called “flavivirus,” affect some 2.5 billion people worldwide and cause hundreds of thousands of deaths each year. There are no antiviral treatments and a just handful of vaccines that provide protection against only a few of these diseases.

The principal investigator for the new five-year study is TSRI Associate Professor Hyeryun Choe, who will lead the effort to understand the virus’s mode of infection and how new therapies might interrupt it.

“Flavivirus uses a very clever method of infection,” Choe said. “It’s like using a side door to enter a house when the front door is locked.”

The viruses take advantage of the process that normally occurs during programmed cell death. During programmed cell death (“apoptosis”), a lipid usually found on the inner side of the cell membranes, specifically phosphatidylserine (PS), shifts to the surface, making itself readily available to any passing cellular stranger. This is where the trouble begins.

When cells are dying from a flavivirus infection, their freshly exposed PS is grabbed by the exiting virus, and phagocytes—cells that devour invading pathogens and dead and dying cells—engulf the virus as if it were a dying cell. Once engulfed by the phagocyte, the virus quickly turns the cell's own biology on its head, forcing it to produce copies of the virus.

While some viruses (influenza A for example) do not use PS in their life cycle, the flavivirus exploits this opportunity to the hilt. Infection of cells by dengue or West Nile viruses is markedly enhanced when phagocytes express receptors that recognize and bind PS.

It appears, however, that flaviviruses use only a subset of these receptors. The high selectivity, and the potency with which some of these receptors promote flavivirus infection, suggest only a small number of receptors might be effectively targeted to treat these diseases.

“We want to understand which PS receptors contribute the most to flavivirus infections and how we might block them,” Choe said. “Our studies are designed to offer insights useful in the development of new therapies.”

http://www.scripps.edu/news/press/2014/20140327choe.html



So Hyreun Choe knows very well about flipped PS and "this is where the trouble begins" but now lets make this connection from HIV <> flipped PS <> over to exosomes and this clearly shows the importance of flipped PS. I have been harping on flipped PS as the biomarker, but Peregrine is digging deeper.... into hundreds of protein level based biomarkers floating out there in the bloodstream. A simple blood test vs those legacy biopsies.

--------------------------------------------

Exosomes and Their Role in the Life Cycle and Pathogenesis of RNA Viruses

Harendra Singh Chahar,1
Xiaoyong Bao,1,2 and
Antonella Casola1,2,*

Yorgo Modis, Academic Editor

1Departments of Pediatrics, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; E-Mails: ude.bmtu@rahahcah (H.S.C.); Email: ude.bmtu@oabix (X.B.)
2Sealy Center for Vaccine Development, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
*Author to whom correspondence should be addressed; E-Mail: ude.bmtu@alosacna; Tel.: +1-409-747-0581; Fax: +1-409-772-1761.

Recent studies on Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), human T-cell lymphotropic virus (HTLV), and Dengue Virus (DENV) have demonstrated that exosomes released from infected cells harbor and deliver many regulatory factors including viral RNA and proteins, viral and cellular miRNA, and other host functional genetic elements to neighboring cells, helping to establish productive infections and modulating cellular responses. Exosomes can either spread or limit an infection depending on the type of pathogen and target cells, and can be exploited as candidates for development of antiviral or vaccine treatments. This review summarizes recent progress made in understanding the role of exosomes in RNA virus infections with an emphasis on their potential contribution to pathogenesis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488737/



Does Patrick Soon-Shiong believe along these lines? Absolutely yes =>> Predictive Protein Pathways ... BUT, he must know all the above that we know, in that flipped PS is where the trouble begins. Remember those two days of Millions of shares traded back in March of 2014 (Soon after this below...) and you think Dr. Soon-Shiong knew back then that flipped PS is where the trouble begins? I say yes and who has 100% lockdown rights to PS Targeting?

Peregrine Pharmaceuticals!

Biotech billionaire's plan to beat cancer
Feb 5, 2014
..
..
Mutations linked to cancer in populations may in reality do nothing in an individual patient, because they aren’t translated into proteins. So each step of the process, from DNA to RNA to proteins, must be validated.

“If it’s not all three, it’s not actionable,” he said.

To get that information, Soon-Shiong invented a new technology for using an old resource of doctors: paraffin-preserved slides of patient tissues. Bouncing laser light off the slides provides information about which proteins are present. Linking that to genomic data gives enough information to characterize what drives the cancer.
http://www.sandiegouniontribune.com/news/2014/feb/05/soon-shiong-cancer-big-data/

Predictive Protein Pathways
http://nanthealth.com/dna-rna-proteins-cancer-drug/

"Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that is the cornerstone of a broad clinical
pipeline."
-- Big Pharmas nightmare... unless they are fortunate enough to have The Bavi Edge!

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