Abstract
TRIM5alpha restriction factors protect target cells from retroviruses by blocking infection prior to the accumulation of viral reverse transcription (RT) products. Here, we demonstrate that heat shock perturbed owl monkey TRIMCyp and rhesus TRIM5alpha-mediated restriction of human immunodeficiency virus type 1 (HIV-1) late RT products and 2-long terminal repeat circles. Heat shock partially rescued HIV-1 infection from TRIMCyp restriction, and this rescue became more profound when combined with the presence of the proteasome inhibitor MG132. This indicates that viral RT products rescued from restriction by either heat shock treatment or the presence of MG132 are on a productive pathway, supporting a model in which TRIM5alpha proteins restrict retroviruses in multiple phases that are differentially sensitive to heat shock and proteasome inhibitors.