N-terminally truncated POM121C inhibits HIV-1 replication.

Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host ch...

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Main Authors: Hideki Saito, Hiroaki Takeuchi, Takao Masuda, Takeshi Noda, Shoji Yamaoka
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5584925?pdf=render
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author Hideki Saito
Hiroaki Takeuchi
Takao Masuda
Takeshi Noda
Shoji Yamaoka
author_facet Hideki Saito
Hiroaki Takeuchi
Takao Masuda
Takeshi Noda
Shoji Yamaoka
author_sort Hideki Saito
collection DOAJ
description Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV) chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1). These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.
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spelling doaj.art-0bb32df872e345fbb7dc78d4253599602022-12-22T03:54:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018243410.1371/journal.pone.0182434N-terminally truncated POM121C inhibits HIV-1 replication.Hideki SaitoHiroaki TakeuchiTakao MasudaTakeshi NodaShoji YamaokaRecent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV) chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1). These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.http://europepmc.org/articles/PMC5584925?pdf=render
spellingShingle Hideki Saito
Hiroaki Takeuchi
Takao Masuda
Takeshi Noda
Shoji Yamaoka
N-terminally truncated POM121C inhibits HIV-1 replication.
PLoS ONE
title N-terminally truncated POM121C inhibits HIV-1 replication.
title_full N-terminally truncated POM121C inhibits HIV-1 replication.
title_fullStr N-terminally truncated POM121C inhibits HIV-1 replication.
title_full_unstemmed N-terminally truncated POM121C inhibits HIV-1 replication.
title_short N-terminally truncated POM121C inhibits HIV-1 replication.
title_sort n terminally truncated pom121c inhibits hiv 1 replication
url http://europepmc.org/articles/PMC5584925?pdf=render
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