Previously, it was demonstrated that increased Gag-Pol levels severely impair virion infectivity through disruption of RNA genome dimerization [62] . Further, HIV protease is known to be toxic to cells as it leads to the production of the novel Procaspase 8 cleavage product, Casp8p41, which induces apoptosis through loss of mitochondrial membrane potential [66] . Therefore, we would expect that virions from CIITA-expressing cells would be reduced in titer and infectivity, as there is increased Gag-Pol and protease. However, while overall viral particle numbers (as measured by p24 ELISA) from CIITA expressing cells were decreased, the infectivity of these virions was significantly increased when calculated by infectious units per pg p24. Interestingly, at 0.6 nM Lopinavir, the infectivity of virions from CIITA-expressing cells increased over vehicle-treated controls, despite reduced Gag processing. Further, the mutants of CIITA, which produced the highest level of Gag-Pol, did not demonstrate a linear increase in Gag processing or virion infectivity, which may be explained by previous work demonstrateing that increased Gag-Pol levels impairs viral infectivity [61, 62] . Therefore it is likely that CIITA is capable of increasing Gag-Pol levels to a point which can impede virus maturation, albeit not enough to reduce it to levels observed from vector-only expressing cells. Therefore, overall infectivity of virions is increased from cells expressing CIITA despite an altered Gag to Gag-Pol ratio. Future studies should focus on how CIITA can increase this ratio without severely impairing virus release as well the novel mechanism by which CIITA increases Gag-Pol levels. Preliminary studies in this laboratory suggest that CIITA enhancement Gag-Pol may be due to increased ribosomal frameshifting (data not shown).