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Review
. 2004 Jan-Jun;10(1-6):1-5.

A hard way to the nucleus

Michael Bukrinsky  1
Affiliations
Review

A hard way to the nucleus

Michael Bukrinsky. Mol Med. 2004 Jan-Jun.

Abstract

As a member of the Retrovirus family, human immunodeficiency virus (HIV), a causative agent of AIDS, replicates by integrating its genome into the host cell's nuclear DNA. However, in contrast to most retroviruses that depend on mitotic dissolution of the nuclear envelope to gain access to the host cell's genome, the HIV pre-integration complex can enter the nucleus of the target cell during the interphase. Such capacity greatly enhances HIV replication and allows the virus to productively infect terminally differentiated nonproliferating cells, such as macrophages. Infection of macrophages is a critical factor in the pathogenesis of diseases caused by HIV-1 and other lentiviruses. The mechanisms responsible for this unusual feature of HIV have enticed researchers since the early 90s, when the first characterization of the HIV-1 pre-integration complex was reported. Several viral factors, including matrix protein, integrase, viral protein R, and central DNA flap, have been proposed as regulators of HIV-1 nuclear import, only to be later shown as nonessential for this process. As a result, after more than a decade of intense research, there is still no consensus on which HIV-1 and cellular proteins control this critical step in HIV-1 replication. In this review, we will discuss recent advances and suggest possible solutions to the controversial issue of HIV-1 nuclear import.

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Figures

Figure 1
Figure 1
Pre-integration steps of HIV-1 replication. Events starting with HIV-1 binding to its main receptors on the target cell, CD4 and CCR5, and ending with viral integration into the host cell’s genome are shown. Proteins packaged into virions are shown; some of these proteins (MA, RT, IN, and Vpr) find their way into the reverse transcription complex (RTC). RTC becomes the pre-integration complex upon completion of reverse transcription. Details of the viral journey through the cytoplasm and into the nucleus are discussed in the text.
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