Cone-shaped HIV-1 Capsids Are Transported Through Intact Nuclear Pores

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 Feb 11

PMID 33571428

Citations 148

Authors

Vojtech Zila

Erica Margiotta

Beata Turonova

Thorsten G Muller

Christian E Zimmerli

Simone Mattei

Matteo Allegretti

Kathleen Borner

Jona Rada

Barbara Muller

Marina Lusic

Hans-Georg Krausslich

Martin Beck

Affiliations

Soon will be listed here.

Abstract

Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import. Here, we combined correlative light and electron microscopy with subtomogram averaging to capture the structural status of reverse transcription-competent HIV-1 complexes in infected T cells. We demonstrated that the diameter of the NPC in cellulo is sufficient for the import of apparently intact, cone-shaped capsids. Subsequent to nuclear import, we detected disrupted and empty capsid fragments, indicating that uncoating of the replication complex occurs by breaking the capsid open, and not by disassembly into individual subunits. Our data directly visualize a key step in HIV-1 replication and enhance our mechanistic understanding of the viral life cycle.

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