HIV integration requires use of a host DNA-repair pathway

Mar 25, 2011

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.

" 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 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.

Explore further: Point-of-care CD4 testing is economically feasible for HIV care in resource-limited areas

Provided by Ohio State University Medical Center

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Study: Cells have a natural defense against HIV

Mar 14, 2006

Scientists here have discovered a previously unknown mechanism that cells use to fight off the human immunodeficiency virus (HIV), the cause of AIDS. The findings indicate that two proteins that normally help repair cellular ...

Deciphering how CD4 T cells die during HIV infection

Nov 24, 2010

Scientists at Gladstone Institute of Virology and Immunology have solved a long-standing mystery about HIV infection–namely how HIV promotes the death of CD4 T cells. It is the loss of this critical subset of immune ...

A cure for HIV could be all in the 'mix'

Aug 18, 2010

Current HIV treatments do not eradicate HIV from host cells but rather inhibit virus replication and delay the onset of AIDS. However, a new research published in BioMed Central's open access journal, AIDS Research & Therapy descri ...

Recommended for you

The genetics of coping with HIV

Sep 16, 2014

We respond to infections in two fundamental ways. One, which has been the subject of intensive research over the years, is "resistance," where the body attacks the invading pathogen and reduces its numbers. Another, which ...

Long acting HIV drugs to be developed

Sep 11, 2014

HIV drugs which only need to be taken once a month are to be developed at the University of Liverpool in a bid to overcome the problem of 'pill fatigue'.

Puerto Rico partners on US HIV vaccine project

Sep 10, 2014

Puerto Rico's governor says the island's largest public university is partnering with federal agencies to oversee a U.S.-funded project aimed at trying to develop a prophylactic vaccine for the HIV virus that causes AIDS.

User comments : 0