Navigation Links
HIV inserts into human genome using a DNA-associated protein

A human DNA-associated protein called LEDGF is the first such molecule found to control the location of HIV integration in human cells, according to a new study from researchers at the University of Pennsylvania School of Medicine.

This study, published in this week's early online edition of Nature Medicine, describes the first clear target for modulating where viruses insert into the human genome, which has implications for better design of gene-therapy delivery. Retroviral vectors are often used to introduce therapeutic genetic sequences into human chromosomes, such as in the delivery of Factor VIII for hemophilia patients.

HIV integrates into active transcription units on chromosomes within the nucleus of human cells. These units are sites that lead to efficient expression of the viral genome. Most HIV-infected cells in a patient will have a very short life span, a day or less. "We surmise that this strategy helps the virus make hay while the sun is shining, as it were, producing lots of viral copies during a short time, so that the virus can maximize production of daughter virions," says Frederic Bushman, PhD, Professor of Microbiology at Penn.

This present study demonstrates the first piece of a mechanism that dictates where HIV integration takes place. Previous studies at other institutions showed that LEDGF binds tightly to HIV integrase, the enzyme that's important for the integration reaction. Now, Penn researchers showed in this study that the way LEDGF binds to HIV integrase and to specific sites on chromosomes suggests that HIV targets integration using a molecular tether.

Retroviruses contain RNA in their particles. They enter a cell and convert RNA into DNA by the enzyme reverse transcriptase and then integrate that DNA copy into the DNA of the host, using the integrase enzyme. The new viral particles are made by transcription of the viral genome, as with any cellular genes. If the cell divides, the viral DNA is copied and inherited, along with cellular human genes.

Bushman and his team made cells that were depleted of LEDGF and found that integration was less frequent in transcription units and in genes regulated by LEDGF. "This implies that LEDGF is part of the machinery that helps dictate the placement of retroviral integration sites within chromosomes," says Bushman.

Bushman notes that finding that LEDGF is part of the cellular apparatus necessary for HIV replication is important to the field of gene therapy. Controlling where gene-therapy vehicles insert in the human genome could help make the delivery of new therapeutic sequences safer. The new findings about LEDGF suggest that engineered tethering interactions might some day allow control over integration site selection during gene therapy. According to Bushman, this finding is of particular importance in light of recent cases where integration of gene-therapy vectors near cancer genes contributed to the development of leukemia in gene-therapy patients.

"This is first example of a cellular factor that's a clear player in target site selection," says Bushman. "This isn't engineering yet, but it's a key piece of information on the way."


'"/>

Source:University of Pennsylvania School of Medicine


Related biology news :

1. Novel technology detects human DNA mutations
2. Current human embryonic stem cell lines contaminated UCSD/Salk team finds
3. UWs Rosetta software to unlock secrets of many human proteins
4. Genome-wide mouse study yields link to human leukemia
5. Found: Missing sequence of the human Y chromosome
6. Study finds more than one-third of human genome regulated by RNA
7. Molecular machine may lead to new drugs to combat human diseases
8. Sea skate experiment sheds light on human cell transport
9. Mouse brain tumors mimic those in human genetic disorder
10. Zebrafish may hold key to understanding human nerve cell development
11. Yale researchers identify molecule for detecting parasitic infection in humans
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/19/2017)... 19, 2017 The global military ... is marked by the presence of several large global ... by five major players - 3M Cogent, NEC Corporation, ... for nearly 61% of the global military biometric market ... the global military biometrics market boast global presence, which ...
(Date:4/11/2017)... GARDENS, Fla. , April 11, 2017 /PRNewswire/ ... management and secure authentication solutions, today announced that ... by Intelligence Advanced Research Projects Activity (IARPA) to ... IARPA,s Thor program. "Innovation has been ... and IARPA,s Thor program will allow us to ...
(Date:4/5/2017)... SEATTLE , April 5, 2017  The Allen ... the Allen Cell Explorer: a one-of-a-kind portal and dynamic ... large-scale 3D imaging data, the first application of deep ... edited human stem cell lines and a growing suite ... the platform for these and future publicly available resources ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ... today it will be hosting a Webinar titled, “Pathology is going digital. Is ... , on digital pathology adoption best practices and how Proscia improves lab economics ...
(Date:10/11/2017)... ... 11, 2017 , ... A new study published in Fertility ... fresh in vitro fertilization (IVF) transfer cycles. The multi-center matched cohort ... After comparing the results from the fresh and frozen transfer cohorts, the authors ...
(Date:10/10/2017)... , ... October 10, 2017 , ... ... Center’s FirstHand program has won a US2020 STEM Mentoring Award. Representatives of the ... for Excellence in Volunteer Experience from US2020. , US2020’s mission is to change ...
(Date:10/10/2017)... ... 10, 2017 , ... USDM Life Sciences , the ... sciences and healthcare industries, announces a presentation by Subbu Viswanathan and Jennifer Jaye ... GxP Validation for Agile Cloud Platforms,” will present a revolutionary approach to achieving ...
Breaking Biology Technology: