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. 2012;3(1):70-85.
Epub 2012 Feb 25.

The HIV-1 passage from cytoplasm to nucleus: the process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration

Kallesh Danappa Jayappa  1 , Zhujun Ao, Xiaojian Yao
Affiliations

The HIV-1 passage from cytoplasm to nucleus: the process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration

Kallesh Danappa Jayappa et al. Int J Biochem Mol Biol. 2012.

Abstract

The human immunodeficiency virus 1 (HIV-1) synthesizes its genomic DNA in cytoplasm as soon as it enters the cell. The newly synthesized DNA remains associated with viral/cellular proteins as a high molecular weight pre-integration complex (PIC), which precludes passive diffusion across intact nuclear membrane. However, HIV-1 successfully overcomes nuclear membrane barrier by actively delivering its DNA into nucleus with the help of host nuclear import machinery. Such ability allows HIV-1 to productively infect non-dividing cells as well as dividing cells at interphase. Further, HIV-1 nuclear import is also found important for the proper integration of viral DNA. Thus, nuclear import plays a crucial role in establishment of infection and disease progression. While several viral components, including matrix, viral protein R, integrase, capsid, and central DNA flap are implicated in HIV-1 nuclear import, their molecular mechanism remains poorly understood. In this review, we will elaborate the role of individual viral factors and some of current insights on their molecular mechanism(s) associated with HIV-1 nuclear import. In addition, we will discuss the importance of nuclear import for subsequent step of viral DNA integration. Hereby we aim to further our understanding on molecular mechanism of HIV-1 nuclear import and its potential usefulness for anti-HIV-1 strategies.

Keywords: HIV-1; capsid; importin; integrase; matrix; nuclear import; viral protein R.

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Figures

Figure 1
Figure 1
The HIV-1 nuclear import machanisms mediated by IN: (A) Virus entry: Receptor mediated membrane fusion of mature virus particle. (B) Uncoating: Disengagement of CA protein molecules from reversetranscription complex in cytoplasm. (C). Pre-integration complex (PIC): The mature HIV-1 nucleoprotein complex waiting for nuclear import. (D). Impα/β mediated nuclear import: The propsed recrutitment of Impα to PIC by IN and subsequent nuclear import by Impα/β mediated classical nuclear import pathway. (E). TNPO3 or Imp7 mediated nuclear import: The propsed recrutitment of TNPO3 or Imp7 by IN and subsequent nuclear import by non-classical nuclear import pathway. (F). Direct interaction with Nups: The proposed nuclear translocation of PIC by direct interaction with Nups without the requirement of soluble factors.
Figure 2
Figure 2
The cellular cytoskeleton and associated components: (A). The actin filaments covering narrow space beneath cytoplasmic membrane and around nucleus. (B). The tubulin filaments covering vast space in cytoplasm between actin filaments. (C). Microtubue organizing center (MTOC): A region in perinuclear compartment marked by microtubule nucleation. (D). Myosin VI: The motor protein complex that mediates retrograde movement of cargos along actin filaments. (E) Dynein: The motor protein complex that mediates retrograde movement of cargos along tubulin filaments.
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