This project was supported by the US National Institutes of Health (AI068462 to K.M.W.) and by the National Cancer Institute, under contracts N01-CO-12400 and HHSN261200800001E (to R.J.G. and J.W.B.). J.M.W. was supported as a Fellow of the UNC Lineberger Cancer Center and a National Institutes of Health (NIH) Kirschstein Postdoctoral Fellowship. R.S. and K.K.D. were supported by NIH grants AI44667 and T32 AI07419, respectively. We are indebted to D. Mathews and J. Low for assistance with the RNA structure program and genome secondary structure analysis, respectively. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations indicate endorsement by the US Government.

Author Contributions J.M.W., R.J.G. and K.M.W. conceived of and designed the HIV-1 genome structure analysis project. J.M.W. and K.M.W. analysed and interpreted the HIV SHAPE structure information. K.K.D., R.S. and C.L.B. designed and performed the bioinformatic pairing probability analysis. J.M.W., R.J.G. and C.W.L. performed the experiments. J.M.W., C.L.B. and K.M.W. performed the statistical analyses. J.W.B. produced and purified HIV-1 virions. J.M.W. and K.M.W. wrote the manuscript with contributions from all authors.