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@ARTICLE{Twizerimana:884114,
      author       = {Twizerimana, Augustin Penda and Scheck, Rachel and Becker,
                      Daniel and Zhang, Zeli and Wammers, Marianne and Avelar,
                      Leandro and Pflieger, Marc and Häussinger, Dieter and Kurz,
                      Thomas and Gohlke, Holger and Münk, Carsten},
      title        = {{C}ell type-dependent escape of capsid inhibitors by simian
                      immunodeficiency virus {SIV}cpz},
      journal      = {Journal of virology},
      volume       = {94},
      number       = {23},
      issn         = {1098-5514},
      address      = {Baltimore, Md.},
      publisher    = {Soc.},
      reportid     = {FZJ-2020-03101},
      pages        = {e01338-20},
      year         = {2020},
      abstract     = {Pandemic human immunodeficiency virus type 1 (HIV-1) is the
                      result of the zoonotic transmission of simian
                      immunodeficiency virus (SIV) from the chimpanzee subspecies
                      Pan troglodytes troglodytes (SIVcpzPtt). The related
                      subspecies Pan troglodytes schweinfurthii is the host of a
                      similar virus, SIVcpzPts, which did not spread to humans. We
                      tested these viruses with small-molecule capsid inhibitors
                      (PF57, PF74, and GS-CA1) that interact with a binding groove
                      in the capsid that is also used by CPSF6. While HIV-1 was
                      sensitive to capsid inhibitors in cell lines, human
                      macrophages, and peripheral blood mononuclear cells (PBMCs),
                      SIVcpzPtt was resistant in rhesus FRhL-2 cells and human
                      PBMCs but was sensitive to PF74 in human HOS and HeLa cells.
                      SIVcpzPts was insensitive to PF74 in FRhL-2 cells, HeLa
                      cells, PBMCs, and macrophages but was inhibited by PF74 in
                      HOS cells. A truncated version of CPSF6 (CPSF6-358)
                      inhibited SIVcpzPtt and HIV-1, while in contrast, SIVcpzPts
                      was resistant to CPSF6-358. Homology modeling of HIV-1,
                      SIVcpzPtt, and SIVcpzPts capsids and binding energy
                      estimates suggest that these three viruses bind similarly to
                      the host proteins cyclophilin A (CYPA) and CPSF6 as well as
                      the capsid inhibitor PF74. Cyclosporine treatment, mutation
                      of the CYPA-binding loop in the capsid, or CYPA knockout
                      eliminated the resistance of SIVcpzPts to PF74 in HeLa
                      cells. These experiments revealed that the antiviral
                      capacity of PF74 is controlled by CYPA in a virus- and cell
                      type-specific manner. Our data indicate that SIVcpz viruses
                      can use infection pathways that escape the antiviral
                      activity of PF74. We further suggest that the antiviral
                      activity of PF74 capsid inhibitors depends on cellular
                      cofactors.IMPORTANCE HIV-1 originated from SIVcpzPtt but not
                      from the related virus SIVcpzPts, and thus, it is important
                      to describe molecular infection by SIVcpzPts in human cells
                      to understand the zoonosis of SIVs. Pharmacological HIV-1
                      capsid inhibitors (e.g., PF74) bind a capsid groove that is
                      also a binding site for the cellular protein CPSF6.
                      SIVcpzPts was resistant to PF74 in HeLa cells but sensitive
                      in HOS cells, thus indicating cell line-specific resistance.
                      Both SIVcpz viruses showed resistance to PF74 in human
                      PBMCs. Modulating the presence of cyclophilin A or its
                      binding to capsid in HeLa cells overcame SIVcpzPts
                      resistance to PF74. These results indicate that early
                      cytoplasmic infection events of SIVcpzPts may differ between
                      cell types and affect, in an unknown manner, the antiviral
                      activity of capsid inhibitors. Thus, capsid inhibitors
                      depend on the activity or interaction of currently
                      uncharacterized cellular factors.},
      cin          = {JSC / NIC / IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
                      I:(DE-Juel1)IBI-7-20200312},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$},
      pid          = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {32907979},
      UT           = {WOS:000595866900008},
      doi          = {10.1128/JVI.01338-20},
      url          = {https://juser.fz-juelich.de/record/884114},
}