RNA splicing patterns contribute to burst size variation among HIV-1-infected Jurkat cell clones

Many models of HIV-1 infection rely on the assumption that actively infected cells release similar amounts of virus, despite recent reports that suggest shedding differs drastically among infected cells. In this study, the expression phenotypes of hundreds of integrant clones were analyzed to identify factors contributing to burst size variation. In agreement with previous reports, virus release spanned over four orders of magnitude within the infected pool. Both proviral expression levels and variation in splicing contributed to these burst size differences. While cell-intrinsic factors appeared to be the primary contributors to heterogeneous shedding patterns, viral point mutations were also observed and, in at least one case, contributed to particle release levels. Together, these findings demonstrate that expression variation among proviruses is both large and multifaceted and suggest that clone-specific differences in HIV-1 expression properties may contribute to unpredicted responses to treatment interventions.