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Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes.

Matreyek KA, Engelman A - Viruses (2013)

Bottom Line: While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid.Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection.In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. alan_engelman@dfci.harvard.edu.

ABSTRACT
Retroviruses integrate their reverse transcribed genomes into host cell chromosomes as an obligate step in virus replication. The nuclear envelope separates the chromosomes from the cell cytoplasm during interphase, and different retroviral groups deal with this physical barrier in different ways. Gammaretroviruses are dependent on the passage of target cells through mitosis, where they are believed to access chromosomes when the nuclear envelope dissolves for cell division. Contrastingly, lentiviruses such as HIV-1 infect non-dividing cells, and are believed to enter the nucleus by passing through the nuclear pore complex. While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid. Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection. In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein.

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Schematic of the nuclear pore complex (NPC) and classical nuclear import pathway. (top) General NPC substructures and locations of nucleoporins (NUPs) that scored as potential HIV-1 co-factors in genome-wide RNA interference screens [17,18,19,20]. Asterisks denote NUPs that scored in more than one screen. (bottom) The Ran-based nuclear import cycle. Import protein cargo binds to a karyopherin (KPN) β protein, oftentimes bridged by a member of the KPN α protein family (KPN β1, which is also referred to as importin β1, and KPN α2 or importin α1, depicted, are canonical members of each protein family). KPN β1 ferries the complex through the NPC channel. The engagement of KPN β1 by Ran-GTP concentrated at the nuclear basket releases the KPN α-cargo complex into the nucleus. KPN β1 becomes free to bind additional import cargo after Ran dissociates from it upon RanBP1 binding and Ran-GTP hydrolysis, stimulated by RanGAP concentrated at the cytoplasmic filaments.
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viruses-05-02483-f001: Schematic of the nuclear pore complex (NPC) and classical nuclear import pathway. (top) General NPC substructures and locations of nucleoporins (NUPs) that scored as potential HIV-1 co-factors in genome-wide RNA interference screens [17,18,19,20]. Asterisks denote NUPs that scored in more than one screen. (bottom) The Ran-based nuclear import cycle. Import protein cargo binds to a karyopherin (KPN) β protein, oftentimes bridged by a member of the KPN α protein family (KPN β1, which is also referred to as importin β1, and KPN α2 or importin α1, depicted, are canonical members of each protein family). KPN β1 ferries the complex through the NPC channel. The engagement of KPN β1 by Ran-GTP concentrated at the nuclear basket releases the KPN α-cargo complex into the nucleus. KPN β1 becomes free to bind additional import cargo after Ran dissociates from it upon RanBP1 binding and Ran-GTP hydrolysis, stimulated by RanGAP concentrated at the cytoplasmic filaments.

Mentions: HIV-1 nucleoprotein complexes are believed to enter the nucleoplasm by passing through nuclear pore complexes (NPCs), which form stable channels through the nuclear envelope during interphase and gate-keep the trafficking of molecules between the cell nucleus and cytoplasm (Figure 1) [3]. Each NPC is composed of ~30 different protein constituents called nucleoporins (NUPs) [4,5,6], which are found in various multiples of eight to yield the 120 MDa tubular structures found in animal cells [7]. Transport through the NPC is highly selective; molecules less than ~9 nm in diameter are able to passively diffuse through the channel, while those up to ~39 nm must be actively transported by interacting with specific carrier proteins [8]. Protein cargos are most often imported by members of the karyopherin (KPN) β superfamily [9]. These proteins pass through the pore by interacting with phenylalanine-glycine (FG) motifs that are found in highly flexible domains present in about one-third of the NUPs and line the inner channel of the NPC structure. Though the precise biophysical mechanism of nuclear transport is not completely understood, it is clear that transport is largely dictated by the properties exerted by these FG-containing domains [10].


Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes.

Matreyek KA, Engelman A - Viruses (2013)

Schematic of the nuclear pore complex (NPC) and classical nuclear import pathway. (top) General NPC substructures and locations of nucleoporins (NUPs) that scored as potential HIV-1 co-factors in genome-wide RNA interference screens [17,18,19,20]. Asterisks denote NUPs that scored in more than one screen. (bottom) The Ran-based nuclear import cycle. Import protein cargo binds to a karyopherin (KPN) β protein, oftentimes bridged by a member of the KPN α protein family (KPN β1, which is also referred to as importin β1, and KPN α2 or importin α1, depicted, are canonical members of each protein family). KPN β1 ferries the complex through the NPC channel. The engagement of KPN β1 by Ran-GTP concentrated at the nuclear basket releases the KPN α-cargo complex into the nucleus. KPN β1 becomes free to bind additional import cargo after Ran dissociates from it upon RanBP1 binding and Ran-GTP hydrolysis, stimulated by RanGAP concentrated at the cytoplasmic filaments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814599&req=5

viruses-05-02483-f001: Schematic of the nuclear pore complex (NPC) and classical nuclear import pathway. (top) General NPC substructures and locations of nucleoporins (NUPs) that scored as potential HIV-1 co-factors in genome-wide RNA interference screens [17,18,19,20]. Asterisks denote NUPs that scored in more than one screen. (bottom) The Ran-based nuclear import cycle. Import protein cargo binds to a karyopherin (KPN) β protein, oftentimes bridged by a member of the KPN α protein family (KPN β1, which is also referred to as importin β1, and KPN α2 or importin α1, depicted, are canonical members of each protein family). KPN β1 ferries the complex through the NPC channel. The engagement of KPN β1 by Ran-GTP concentrated at the nuclear basket releases the KPN α-cargo complex into the nucleus. KPN β1 becomes free to bind additional import cargo after Ran dissociates from it upon RanBP1 binding and Ran-GTP hydrolysis, stimulated by RanGAP concentrated at the cytoplasmic filaments.
Mentions: HIV-1 nucleoprotein complexes are believed to enter the nucleoplasm by passing through nuclear pore complexes (NPCs), which form stable channels through the nuclear envelope during interphase and gate-keep the trafficking of molecules between the cell nucleus and cytoplasm (Figure 1) [3]. Each NPC is composed of ~30 different protein constituents called nucleoporins (NUPs) [4,5,6], which are found in various multiples of eight to yield the 120 MDa tubular structures found in animal cells [7]. Transport through the NPC is highly selective; molecules less than ~9 nm in diameter are able to passively diffuse through the channel, while those up to ~39 nm must be actively transported by interacting with specific carrier proteins [8]. Protein cargos are most often imported by members of the karyopherin (KPN) β superfamily [9]. These proteins pass through the pore by interacting with phenylalanine-glycine (FG) motifs that are found in highly flexible domains present in about one-third of the NUPs and line the inner channel of the NPC structure. Though the precise biophysical mechanism of nuclear transport is not completely understood, it is clear that transport is largely dictated by the properties exerted by these FG-containing domains [10].

Bottom Line: While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid.Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection.In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. alan_engelman@dfci.harvard.edu.

ABSTRACT
Retroviruses integrate their reverse transcribed genomes into host cell chromosomes as an obligate step in virus replication. The nuclear envelope separates the chromosomes from the cell cytoplasm during interphase, and different retroviral groups deal with this physical barrier in different ways. Gammaretroviruses are dependent on the passage of target cells through mitosis, where they are believed to access chromosomes when the nuclear envelope dissolves for cell division. Contrastingly, lentiviruses such as HIV-1 infect non-dividing cells, and are believed to enter the nucleus by passing through the nuclear pore complex. While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid. Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection. In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein.

Show MeSH
Related in: MedlinePlus