Virus

Nucleus

Nuclear transport

Structural engineering

Biology

Gene

Biophysics

Engineering

Viral replication

Reverse transcriptase

Virology

Chemistry

Capsid

Cell nucleus

Cell biology

Structural integrity

Human immunodeficiency virus (HIV)

Biochemistry

Group-specific antigen

Proceedings of the National Academy of Sciences

Significance Here, we used a fluorescent protein that is free in solution and is trapped in nuclear HIV-1 capsids to demonstrate that the capsids retain integrity and prevent mixing of macromolecules within the viral core and the cellular environment until just before integration. We also found that capsid integrity is maintained until just minutes before disassembly in the nucleus, revealing that uncoating proceeds rapidly after integrity loss. These valuable insights into the early stage of HIV-1 replication indicate that intact HIV-1 capsids are imported through nuclear pores, that reverse transcription is mostly completed within intact capsids, and that preintegration complex-host interactions facilitating integration and target site selection must occur within a short time frame between capsid disassembly and integration.

HIV-1 cores retain their integrity until minutes before uncoating in the nucleus