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SUN1 regulates HIV-1 nuclear import in a manner dependent on the interaction between the viral capsid and cellular cyclophilin A.

SUN1 regulates HIV-1 nuclear import in a manner dependent on the interaction between the viral capsid and cellular cyclophilin A.
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Luo X, Yang W, Gao G,


Luo X, Yang W, Gao G, (click to view)

Luo X, Yang W, Gao G,

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Journal of virology 2018 04 11() pii 10.1128/JVI.00229-18

Abstract

HIV-1 can infect non-dividing cells via passing through the nuclear pore complex. The nuclear membrane imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here, we report that overexpression of SUN1 specifically inhibited the infection of HIV-1, but not simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription, but led to reduced accumulation of the 2-LTR circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for the viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine A (CsA) significantly reduced the sensitivity of the virus to SUN1 and an HIV-1 mutant containing CA-G89A that does not interact with cyclophilin A (CypA) was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wildtype virus, but not the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA.HIV-1 infects both dividing and non-dividing cells. The viral pre-integration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of the nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1; the regulatory activity of SUN1 towards HIV-1 relied on the interaction between CA and CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear entry process.

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