PIM1 and PIM3 Kinases Suppress HIV-1 Protein Expression and Particle Production Through Distinct Roles

PIM kinases (PIM1, PIM2, PIM3) are serine/threonine kinases implicated in infection and reactivation of various viruses, but their roles in HIV-1 gene expression and particle production remain unclear. We examined their impact on HIV-1 and related viruses using co-transfection systems. PIM1 and PIM3, but not PIM2, markedly suppressed HIV-1 virion production without affecting infectivity. This inhibitory effect extended to transmitted/founder HIV-1 clones and SIV, indicating broad activity across lentiviruses. Kinase-dead mutants failed to reduce virion production, confirming the requirement for catalytic activity. Our data suggest that PIM1 and PIM3 act at distinct steps of HIV-1 gene expression: PIM1 reduces transcription, whereas PIM3 acts post-transcriptionally to diminish viral protein expression. Co-expression of PIM1 and PIM3 further enhanced suppression, suggesting complementary functions. Both kinases also inhibited expression from non-LTR promoters, implying involvement of general cellular factors. These findings reveal distinct and cooperative actions of PIM1 and PIM3 in limiting HIV-1 particle production, providing new insights into host kinase-mediated regulation of viral gene expression.