Navigation Links
Mayo researchers discover HIV dependence on a human protein

Mayo Clinic virologists have discovered that a specific human protein is essential for HIV to integrate into the human genome. Their findings show that when HIV inserts itself into a chromosome, a key step that enables it to establish a "safe haven," it requires a specific protein -- LEDGF/p75 (p75). This protein forms a molecular tether between chromosomes and HIV's integrating protein (integrase). If the connection can be disrupted in the future, it might lead to new therapy for HIV or safer methods of gene therapy. The details appear today in the journal Science.

"How an incoming virus co-opts the cell's assistance as it proceeds to establish its permanently integrated state is a fascinating question," says Eric Poeschla, M.D., the Mayo Clinic virologist who led the research. "It's critical to understand this better because permanently integrated viruses in long-lived cells prevent elimination of HIV. In the future, it will be of interest to examine whether HIV's dependence on p75 can be exploited therapeutically."

How They Did It

The researchers started by noticing that p75 "tethers" HIV integrase to human chromosomes like a molecular rope and also protects it from the cell's protein-degrading machinery. While these were provocative findings, what they meant for the whole virus was unclear.

The Mayo team then developed a highly effective version of a technique called "RNA interference" to strip all detectable p75 from human chromosomes. Without its p75 partner, HIV was highly impaired. An intriguing irony is their use of a crippled version of HIV itself, a virus with proven skill in accessing the human genome, to deliver the RNA interference. As a result, human T cells, HIV's main target, became resistant to HIV. Adding back p75 made them vulnerable again. And adding a "dominant-negative" piece of p75 to the mix, a sort of molecular spanner in the works, further impaired the virus (over 500-fold).

Moreover, the Mayo team showed that each "knot" of the molecular tether was necessary, defining the mechanism in a way an artist would delineate the knots at each end of the rope that links a tetherball to a pole.

"It turns out that the virus needs surprisingly little p75 to integrate," says Dr. Poeschla. "Future studies will want to factor such potential potency into designs of screens for additional key cellular proteins that HIV either appropriates as partners, as in the case of p75, or schemes to evade. Quite a few more likely exist. The challenge is to use the right methods to find them."

How HIV Infects Humans -- Cannot Currently Be Eradicated

Each time HIV reproduces itself, it uses its integrase protein to insert a copy of its genome into a chromosome. That copy becomes a permanent archive of the virus's genetic program, like a tiny file burned onto a computer hard drive. While patients are kept healthy when those copies are "suppressed" with multiple daily antiviral medicines, they are never cured. Stopping the medicines even briefly lets HIV repopulate the body with many millions of copies, like a computer virus spreading around the world from a single infected computer.


'"/>

Source:Mayo Clinic


Related biology news :

1. NYU researchers simulate molecular biological clock
2. Vital step in cellular migration described by UCSD medical researchers
3. ASU researchers finds novel chemistry at work to provide parrots vibrant red colors
4. UCSD researchers maintain stem cells without contaminated animal feeder layers
5. Why do insects stop breathing? To avoid damage from too much oxygen, say researchers
6. New protein discovered by Hebrew University researchers
7. First real-time view of developing neurons reveals surprises, say Stanford researchers
8. Agilent Technologies releases automated literature search tool for biology researchers
9. Self-assembled nano-sized probes allow Penn researchers to see tumors through flesh and skin
10. Yale researchers identify molecule for detecting parasitic infection in humans
11. US life expectancy about to decline, researchers say
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/3/2016)... , May 3, 2016  Neurotechnology, a ... the MegaMatcher Automated Biometric Identification System (ABIS) ... large-scale multi-biometric projects. MegaMatcher ABIS can process multiple ... using any combination of fingerprint, face or iris ... MegaMatcher SDK and MegaMatcher Accelerator , ...
(Date:4/19/2016)... April 20, 2016 The new ... a compact web-based "all-in-one" system solution for all door ... reader or the door interface with integration authorization management ... control systems. The minimal dimensions of the access control ... the building installations offer considerable freedom of design with ...
(Date:3/31/2016)...   LegacyXChange, Inc. ... LegacyXChange is excited to release its first ... be launched online site for trading 100% guaranteed authentic ... also provide potential shareholders a sense of the value ... industry that is notorious for fraud. The video is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... MONICA, Calif. , June 23, 2016  The Prostate Cancer Foundation ... pioneer increasingly precise treatments and faster cures for prostate cancer. Members of the ... institutions across 15 countries. Read More About the Class ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample tracking software company, ... Crime Laboratory, has joined STACS DNA as a Field Application Specialist. , “I ... President and COO of STACS DNA. “In further expanding our capacity as a scientific ...
(Date:6/23/2016)... Andrew D Zelenetz ... Published recently in Oncology ... touchONCOLOGY, Andrew D Zelenetz , discusses the ... is placing an increasing burden on healthcare systems ... With the patents on many biologics expiring, interest ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity Products, a division of ... and optimized exclusively for Okuma CNC machining centers at The International Manufacturing Technology ... among several companies with expertise in toolholding, cutting tools, machining dynamics and distribution, ...
Breaking Biology Technology: