The human immunodeficiency virus type 1 Rev protein: ménage à trois during the early phase of the lentiviral replication cycle

Bastian Grewe,Klaus Überla

doi:10.1099/vir.0.022509-0

Abstract

The Rev protein of human immunodeficiency viruses (HIV) has long been recognized to be essential for the late phase of the virus replication cycle, due to its strong enhancement of expression of viral structural proteins. Surprisingly, a number of recent papers have demonstrated that Rev can also interfere with integration of the reverse-transcribed cDNA into the host-cell genome. This seems to be due to Rev's binding to integrase and LEDGF/p75, an important cellular cofactor of HIV-1 integration. As Rev is presumably expressed at sufficiently high levels only after the encoding genome has already integrated, the main function of Rev during the early phase might be to reduce genotoxicity due to excessive integration events after superinfection of the same cell by subsequent viruses. Other potential consequences for HIV-1 replication and evolution after co-infection of the same cell with two viruses are discussed.

Highlights

The retrovirus replication cycle starts with the entry of the virus into the host cell, followed by reverse transcription of the genomic viral RNA into viral cDNA
Transcription of the integrated proviral DNA marks the start of the late phase, which includes the subsequent splicing and trafficking events of the viral RNAs as well as translation, assembly and budding (Freed, 2001)
By binding to the Rev-responsive element (RRE), an RNA structure present on the unspliced RNA encoding Gag and GagPol and on singly spliced RNAs encoding Env, Rev tethers these transcripts to the cellular CRM-1-mediated nuclear-export pathway, leading to enhanced cytoplasmic levels of these RNAs and increased expression of the encoded proteins. This nuclear-export function does not seem to be the only effect of Rev during the late phase of the virus replication cycle

Summary

Bastian Grewe and Klaus Uberla

The Rev protein of human immunodeficiency viruses (HIV) has long been recognized to be essential for the late phase of the virus replication cycle, due to its strong enhancement of expression of viral structural proteins. A number of recent papers have demonstrated that Rev can interfere with integration of the reverse-transcribed cDNA into the host-cell genome. This seems to be due to Rev’s binding to integrase and LEDGF/p75, an important cellular cofactor of HIV-1 integration. As Rev is presumably expressed at sufficiently high levels only after the encoding genome has already integrated, the main function of Rev during the early phase might be to reduce genotoxicity due to excessive integration events after superinfection of the same cell by subsequent viruses.

Introduction

Findings

Mechanisms of the regulatory role of Rev during the early phase