Cyclophilin A-Dependent Restriction of Human Immunodeficiency Virus Type 1 Capsid Mutants for Infection of Nondividing Cells

摘要: Among retroviruses, lentiviruses are unusual in their ability to efficiently infect both dividing and nondividing cells, such as activated T cells macrophages, respectively. Recent studies implicate the viral capsid protein (CA) a key determinant of cell-cycle-independent infection by human immunodeficiency virus type 1 (HIV-1). We investigated effects host cell cyclophilin A (CypA), which binds HIV-1 CA, on cells. The CA mutants A92E, T54A, R132K were impaired for aphidicolin-arrested HeLa but not HOS synthesized normal quantities two-long-terminal-repeat circles arrested indicating that mutant preintegration complexes can enter nuclei infectivity was relieved either pharmacological or genetic disruption CypA-CA interaction RNA interference-mediated depletion CypA expression target second-site suppressor CypA-restricted phenotype also restored growth-arrested These results indicate specifically at step between nuclear import integration This study reveals novel cell-specific restriction is dependent interactions.