Whole-Genome Characterization of Human and Simian Immunodeficiency Virus Intrahost Diversity by Ultradeep Pyrosequencing

Rapid evolution and high intrahost sequence diversity are hallmarks of human and simian immunodeficiency virus (HIV/SIV) infection. Minor viral variants have important implications for drug resistance, receptor tropism, and immune evasion. Here, we used ultradeep pyrosequencing to sequence complete HIV/SIV genomes, detecting variants present at a frequency as low as 1%. This approach provides a more complete characterization of the viral population than is possible with conventional methods, revealing low-level drug resistance and detecting previously hidden changes in the viral population. While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen.National Institutes of Health (NIH)[R21 AI068488-02]National Institutes of Health (NIH)[R21AI073230-02]National Institutes of Health (NIH)[R01 AI077376]National Institutes of Health (NIH)[GM-43940]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/15856-9]National Center for Research Resources (NCRR), NIH[P51 RR000167]National Center for Research Resources (NCRR), NIH[P40 RR019995]University of Wisconsin-MadisonUniversity of Wisconsin School of Medicine and Public Health Medical Education and Research Committee[233KA28]Research Facilities Improvement Program[RR15459-01]Research Facilities Improvement Program[RR020141-01