The infection of cells by human immunodeficiency virus type 1 (HIV-1) can be restricted by host factors through a variety of mechanisms. Identification and characterization of restriction factors against HIV-1 help to explain why effective HIV-1 infection can be established in certain types of cells but not in others, and suggest new approaches to the control of HIV-1 infection.

Professor Guangxia Gao at the Institute of Biophysics, Chinese Academy of Sciences and co-workers recently discovered that the zinc-finger antiviral protein (ZAP) inhibits HIV-1 infection. Unlike the previously reported restriction factors against HIV-1, both human and rat ZAP inhibited the propagation of replication-competent HIV-1, suggesting that ZAP is neither species-specific nor antagonized by HIV-1 protein.

Further analysis demonstrated that ZAP inhibits HIV-1 replication by degrading HIV-1 mRNA. There are three types of HIV-1 mRNA: unspliced, singly spliced and multiply spliced. Specifically, ZAP recognizes and targets the multiply spliced HIV-1 mRNA for degradation from both ends by recruits mRNA degradation machineries.

These results reveal a new mechanism against HIV-1 in host cells and suggest that HIV-1 mRNA is a potential drug target for HIV-1 control.

This work was published in the latest issue of PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2011,108 (38):15834-15839.