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N-terminally truncated POM121C inhibits HIV-1 replication

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  • Hideki Saito
  • Hiroaki Takeuchi
  • Takao Masuda
  • Takeshi Noda
  • Shoji Yamaoka

Abstract

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.

Suggested Citation

  • Hideki Saito & Hiroaki Takeuchi & Takao Masuda & Takeshi Noda & Shoji Yamaoka, 2017. "N-terminally truncated POM121C inhibits HIV-1 replication," PLOS ONE, Public Library of Science, vol. 12(9), pages 1-23, September.
    • Handle: RePEc:plo:pone00:0182434
    DOI: 10.1371/journal.pone.0182434
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    1. David M. Sayah & Elena Sokolskaja & Lionel Berthoux & Jeremy Luban, 2004. "Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1," Nature, Nature, vol. 430(6999), pages 569-573, July.
    2. Jane Rasaiyaah & Choon Ping Tan & Adam J. Fletcher & Amanda J. Price & Caroline Blondeau & Laura Hilditch & David A. Jacques & David L. Selwood & Leo C. James & Mahdad Noursadeghi & Greg J. Towers, 2013. "HIV-1 evades innate immune recognition through specific cofactor recruitment," Nature, Nature, vol. 503(7476), pages 402-405, November.
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