Navigation Links
HIV integration requires use of a host DNA-repair pathway

COLUMBUS, Ohio The human immunodeficiency virus (HIV), the cause of AIDS, makes use of the base excision repair pathway when inserting its DNA into the host-cell genome, according to a new study led by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Crippling the repair pathway prevents the virus from completing this critical step in the retrovirus's life cycle.

The findings offer potential new targets for novel anti-HIV drugs that may not lead as quickly to viral resistance as current drugs, the researchers say.

"HIV continues to develop resistance to current therapies," says first author Kristine Yoder, assistant professor of molecular virology, immunology and medical genetics. "But the proteins we talk about in this paper are made by the cell, so drugs that target them might not lead to resistance as quickly as drugs that target viral proteins. And while targeting host proteins does have the potential for side effects, studies of mice suggest that targeting some of these genes may not lead to significant side effects."

The paper was published online March 23 in the journal PLoS ONE.

Cells normally use base excision repair to fix oxidative damage to DNA caused by reactive molecules such as hydrogen peroxide and oxygen radicals, which form during energy production and other metabolic processes.

For this study, Yoder and her colleagues investigated the role of the repair pathway in the virus insertion process by engineering four strains of mouse fibroblast cells that each lacked a component of the pathway. Specifically, they deleted genes for three glycosylase enzymes Ogg1, Myh, and Neil1 and one polymerase gene, Pol-beta.

They found that the loss of any of these elements reduced the ability of HIV DNA to integrate with host-cell DNA by about 60 to 70 percent. In an additional experiment, the researchers restored the polymerase in cells that lacked it, and this enabled the HIV DNA to again integrate at its normal level.

"Overall, our findings indicate that HIV infection and integration efficiency depends on the presence of base excision repair proteins, and that these proteins might make novel new targets for the treatment of HIV infection," Yoder says.


Contact: Darrell E. Ward
Ohio State University Medical Center

Related biology news :

1. Mandate for biofuels production requires science-based policy and global perspective
2. Growth of new brain cells requires epigenetic switch
3. Long-term recovery of reefs from bleaching requires local action to increase resilience
4. Study finds DNA barcoding requires caution without closer examination
5. IPY follow-up requires year-round research on Arctic and global warming
6. Early cotton planting requires irrigation
7. Killing drug-resistant melanoma requires combination therapy
8. Breast cancer treatment resistance linked to signaling pathway
9. Barcelona Declaration 2008: Challenges and Pathways to Earth Sustainability
10. Research uncovers new steps on pathway to enlarged heart
11. New gene-silencing pathway found in plants
Post Your Comments:
(Date:11/12/2015)... , Nov. 12, 2015  A golden retriever ... Duchenne muscular dystrophy (DMD) has provided a new lead ... Children,s Hospital, the Broad Institute of MIT and Harvard ... Brazil . Cell, pinpoints ... dogs "escape" the disease,s effects. The Boston Children,s lab ...
(Date:11/10/2015)... NEW YORK , Nov. 10, 2015 /PRNewswire/ ... refers to behavioral biometrics that helps to identify ... prevent fraud. Signature is considered as the secure ... for the identification of a particular individual because ... offers more accurate results especially when dynamic signature ...
(Date:10/29/2015)... , Oct. 29, 2015   MedNet Solutions , ... entire spectrum of clinical research, is pleased to announce ... Tech Association (MHTA) as one of only three finalists ... "Software – Small and Growing" category. The Tekne Awards honor ... have shown superior technology innovation and leadership. ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... HOLLISTON, Mass. , Nov. 25, 2015 ... a biotechnology company developing bioengineered organ implants for life-threatening ... will present at the LD Micro "Main Event" investor ... PT. The presentation will be webcast live and posted ... also be available at the conference for one-on-one meetings ...
(Date:11/25/2015)... 2015 Orexigen® Therapeutics, Inc. (Nasdaq: OREX ... fireside chat discussion at the Piper Jaffray 27th Annual ... The discussion is scheduled for Wednesday, December 2, at ... A replay will be available for 14 days after ... Julie NormartVP, Corporate Communications and Business Development , BrewLife(858) ...
(Date:11/24/2015)... ... ... The United States Golf Association (USGA) today announced Dr. Bruce Clarke, of ... since 1961, the USGA Green Section Award recognizes an individual’s distinguished service to the ... of Iselin, N.J., is an extension specialist of turfgrass pathology in the department of ...
(Date:11/24/2015)... Worcester, Mass. (PRWEB) , ... November 24, 2015 ... ... need to maintain healthy metabolism. But unless it is bound to proteins, copper ... Institutes of Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a ...
Breaking Biology Technology: