Transportin 3 and importin α are required for effective nuclear import of HIV-1 integrase in virus-infected cells

Levin, Aviad; Hayouka, Zvi; Friedler, Assaf; Loyter, Abraham

doi:10.4161/nucl.1.5.12903

Cited by 37 publications

(30 citation statements)

References 66 publications

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“…However, LEDGF might be involved in nuclear import in either an NLS-dependent or -independent manner. More intense studies are needed to confirm its genuine role in the lentiviral life cycle (Llano et al 2004a;Levin et al 2010aLevin et al , 2011.…”

Section: Ledgfmentioning

confidence: 99%

“…The depletion of importin ␣3 decreases 2-LTR levels (Ao et al 2010). Both TNPO3 and importin ␣1 (Rch1), acting concurrently or independently, are required for successful nuclear import of IN (Levin et al 2010a). Another homolog, importin 7, was thought to be dispensable in HIV-1-or SIV-infected macrophages (Zielske and Stevenson 2005).…”

Section: Karyopherins and Tnpo3mentioning

confidence: 99%

“…Nuclear localization of overexpressed full-length IN and disability in 2-LTR production by IN CTD deletion mutants provide strong evidence of its karyophilic role. Recent studies show that the IN CTD interacts with both importin ␣3 and importin 7, as well as with TNPO3, for passage through the NPC (Levin et al 2010a). The import mediated by the IN CTD-importin 7 interaction is specific for digitonin-permeabilized cell systems.…”

Section: Integrasementioning

confidence: 99%

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Cellular and viral determinants of retroviral nuclear entry

2016

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Retroviruses must integrate their cDNA into the host genome to generate proviruses. Viral DNA-protein complexes interact with cellular proteins and produce pre-integration complexes, which carry the viral genome and cross the nuclear pore channel to enter the nucleus and integrate viral DNA into host chromosomal DNA. If the reverse transcripts fail to integrate, linear or circular DNA species such as 1-and 2-long terminal repeats are generated. Such complexes encounter numerous cellular proteins in the cytoplasm, which restrict viral infection and protect the nucleus. To overcome host cell defenses, the pathogens have evolved several evasion strategies. Viral proteins often contain nuclear localization signals, allowing entry into the nucleus. Among more than 1000 proteins identified as required for HIV infection by RNA interference screening, karyopherins, cleavage and polyadenylation specific factor 6, and nucleoporins have been predominantly studied. This review discusses current opinions about the synergistic relationship between the viral and cellular factors involved in nuclear import, with focus on the unveiled mysteries of the host-pathogen interaction, and highlights novel approaches to pinpoint therapeutic targets.

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Section: Ledgfmentioning

confidence: 99%

Section: Karyopherins and Tnpo3mentioning

confidence: 99%

Section: Integrasementioning

confidence: 99%

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Cellular and viral determinants of retroviral nuclear entry

2016

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“…he host factor TNPO3 is required for the infection of several lentiviruses (1,3,9,10,13,19,21). To assess the role of TNPO3 in retroviral infection, we stably knocked down TNPO3 expression in HeLa cells by transduction of the pLKO.1-shRNA vector that specifically targets the TNPO3 transcript.…”

mentioning

confidence: 99%

TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core

Valle-Casuso

Nunzio

Yang

et al. 2012

J Virol

105

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dTNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to integration. To investigate the mechanistic requirement of TNPO3 in HIV-1 infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3 binds to the HIV-1 core. Overall, this work suggests that TNPO3 interacts with the incoming HIV-1 core in the cytoplasm to assist a process that is important for HIV-1 infection after nuclear import.

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“…41) Here, we assumed that the NLS of PFV IN interacts with TNPO3 that direct the nuclear import of incoming viral DNA. Earlier studies demonstrated that nuclear import of HIV-1 IN is mediated by interacting with host protein TNPO3, 2,3) importin α/β, 42) and lens epithelium-derived growth factor (LEDGF/p75) for targeting viral DNA to the host chromosome. 43) A putative bipartite NLS of HIV-1 IN has been reported to facilitate the interaction between IN and karyopherin α.…”

Section: )mentioning

confidence: 99%

Knockdown of the host cellular protein transportin 3 attenuates prototype foamy virus infection

Ali¹,

Kim²,

Hamid³

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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Transportin 3 (TNPO3) is a member of the importin-ß superfamily proteins. Despite numerous studies, the exact molecular mechanism of TNPO3 in retroviral infection is still controversial. Here, we provide evidence for the role and mechanism of TNPO3 in the replication of prototype foamy virus (PFV). Our findings revealed that PFV infection was reduced 2-fold by knockdown (KD) of TNPO3. However, late stage of viral replication including transcription, translation, viral assembly, and release was not influenced. The differential cellular localization of PFV integrase (IN) in KD cells pinpointed a remarkable reduction of viral replication at the nuclear import step. We also found that TNPO3 interacted with PFV IN but not with Gag, suggesting that IN-TNPO3 interaction is important for nuclear import of PFV pre-integration complex. Our report enlightens the mechanism of PFV interaction with TNPO3 and support ongoing research on PFV as a promising safe vector for gene therapy.

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Transportin 3 and importin α are required for effective nuclear import of HIV-1 integrase in virus-infected cells

Cited by 37 publications

References 66 publications

Cellular and viral determinants of retroviral nuclear entry

Cellular and viral determinants of retroviral nuclear entry

TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core

Knockdown of the host cellular protein transportin 3 attenuates prototype foamy virus infection

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