A Phenotypic Recessive, Post‐Entry Block in Rabbit Cells that Results in Aberrant Trafficking of HIV‐1

Rabbit cells are poorly permissive to HIV-1 infection, but little is known about the nature of this block. Here, we show that the block to infection is mainly at the level of reverse transcription (RT), is independent of the cell receptor used by the virus for entry, cannot be effectively saturated with high doses of virus or virus-like particles, and has a recessive phenotype in human-rabbit heterokaryons. RT complexes (RTCs) extracted from human and rabbit cells have different densities but are both competent for RT in an in vitro endogenous assay. Cell fractionation showed that HIV-1 is trafficked in a different way in human and rabbit cells and that correct intracellular trafficking is linked to efficient RT and high infectivity in vivo. Viral DNA accumulated in rabbit cell nuclei only at a later stage and failed to associate with chromatin, suggesting a further block prior to integration. Our data point to the existence of cellular factors regulating the early stages of intracytoplasmic and possibly intranuclear HIV-1 trafficking.