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:

(Date:6/22/2016)... LOS ANGELES , June 22, 2016 ... of identity management and verification solutions, has ... cutting edge software solutions for Visitor Management, ... ® provides products that add functional ... The partnership provides corporations and venues with ...
(Date:6/15/2016)... New York , June 15, 2016 /PRNewswire/ ... a new market report titled "Gesture Recognition Market by ... and Forecast, 2016 - 2024". According to the report, ... USD 11.60 billion in 2015 and is estimated ... reach USD 48.56 billion by 2024.  ...
(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ("Biorem" ... by its major shareholders, Clean Technology Fund I, LP ... States based venture capital funds which together ... (on a fully diluted, as converted basis), that they ... their entire equity holdings in Biorem to TUS Holdings ...
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. Hoffmann, ... faculty of the University of North Carolina Kenan-Flagler Business School effective ... at UNC Kenan-Flagler, with a focus on the school’s international efforts, leading classes ...
(Date:6/24/2016)... ... ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension of 8.5 ... end machines that use the more unconventional z-dimension of 20mm. Z-dimension or ... the cuvette holder. , FireflySci has developed several Agilent flow cell product lines ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT ... Ontario biotechnology company, Propellon Therapeutics ... development and commercialization of a portfolio of first-in-class ... Epigenetic targets such as WDR5 represent an exciting ... significantly in precision medicine for cancer patients. Substantial ...
Breaking Biology Technology: