Lentiviral nuclear import: a complex interplay between virus and host

Abstract

Although the capacity to infect non-dividing cells is a hallmark of lentiviruses, nuclear import is still barely understood. More than 100 research papers have been dedicated to this topic during the last 15 years, yet, more questions have been raised than answers. The signal-facilitating translocation of the viral preintegration complex (PIC) through the nuclear pore complex (NPC) remains unknown. It is clear, however, that nuclear import is the result of a complex interplay between viral and cellular components. In this review, we discuss the current knowledge on nuclear import. We focus on the controversies and pitfalls and discuss the interplay between virus and host.

Cellular Restriction Targeting Viral Capsids Perturbs Human Immunodeficiency Virus Type 1 Infection of Nondividing Cells

“…Previous studies in this field were directed at HIV-1-encoded molecules (e.g., matrix, Vpr, integrase, and cPPT) that harbor nuclear import activity (9,39). However, our laboratory demonstrated that none of the previously reported karyophilic elements encoded by HIV-1 is essential for the cell cycle independence of HIV infection (44).…”

Identification of Residues in the C-terminal Domain of HIV-1 Integrase That Mediate Binding to the Transportin-SR2 Protein

“…Here, we studied the molecular interaction between TRN-SR2 and HIV-1 IN to define the NLS in IN. Because IN has been proposed before to play a role in HIV nuclear import (5,6,11,12,50) (31). Multiple IN mutations were inserted into viruses and tested for their impact on viral replication.…”

“…After virus entry and reverse transcription, the preintegration complex (PIC) 5 translocates to the nucleus, and the viral DNA is integrated into the host chromatin. HIV crosses the nuclear membrane through active nuclear import of the PIC (3).…”

“…Until recently, the mechanism of HIV nuclear import, albeit intensely studied, remained obscure (for recent reviews see Refs. 5,6). Several viral elements, including matrix, viral protein R, capsid, IN, and the central polypurine tract have been suggested to play a role in the nuclear import of HIV (5,(7)(8)(9)(10).…”

“…5,6). Several viral elements, including matrix, viral protein R, capsid, IN, and the central polypurine tract have been suggested to play a role in the nuclear import of HIV (5,(7)(8)(9)(10). Next to different viral components, multiple nuclear import factors have been implicated in the nuclear translocation of the PIC, such as importin-␣/␤ (11-13), importin-7 (14 -16), and importin-␣3 (17).…”