Natural antisense transcripts (NATs) represent a class of RNA molecules that are transcribed from the opposite strand of a protein-coding gene, and that have the ability to regulate the expression of their cognate protein-coding gene via multiple mechanisms. NATs have been described in many prokaryotic and eukaryotic systems, as well as in the viruses that infect them. The human immunodeficiency virus (HIV-1) is no exception, and produces one or more NAT from a promoter within the 3' long terminal repeat. HIV-1 antisense transcripts have been the focus of several studies spanning over 30 years. However, a complete appreciation of the role that these transcripts play in the virus lifecycle is still lacking. In this review, we cover the current knowledge about HIV-1 NATs, discuss some of the questions that are still open and identify possible areas of future research.
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