艾滋病毒传播依赖于宿主碱基切除修复

The human immunodeficiency virus (HIV), the cause of AIDS, makes use of the base excision¹ repair（切补修复） pathway when inserting its DNA² 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.

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"HIV continues to develop resistance to current therapies," says first author Kristine Yoder, assistant professor of molecular³ virology（病毒学） , 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 genes⁵ may not lead to significant side effects."

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

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Cells normally use base excision repair to fix oxidative（氧化的） damage to DNA caused by reactive molecules⁶ such as hydrogen peroxide and oxygen radicals⁷, which form during energy production and other metabolic⁸ 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（纤维原细胞） cells that each lacked a component⁹ of the pathway. Specifically, they deleted genes for three glycosylase enzymes¹⁰ – Ogg1, Myh, and Neil1 – and one polymerase gene⁴, 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 integration¹¹ 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.