title: The highly polymorphic cyclophilin A-binding loop in HIV-1 capsid modulates viral resistance to MxB.
abstract: BACKGROUND
  The human myxovirus-resistance protein B (MxB, also called Mx2) was recently reported to inhibit HIV-1 infection by impeding the nuclear import and integration of viral DNA. However, it is currently unknown whether there exist MxB-resistant HIV-1 strains in the infected individuals. Answer to this question should address whether MxB exerts an inhibitory pressure on HIV-1 in vivo and whether HIV-1 has evolved to evade MxB inhibition.
  
  
  RESULTS
  We have examined ten transmitted founder (T/F) HIV-1 strains for their sensitivity to MxB inhibition by infecting CD4+ T cell lines SupT1 and PM1 that were stably transduced to express MxB. Two T/F stains, CH040.c and RHPA.c, were found resistant and this resistance phenotype was mapped to the amino acid positions 87 and 208 in viral capsid. The H87Q mutation is located in the cyclophilin A (CypA) binding loop and has a prevalence of 21% in HIV-1 sequences registered in HIV database. This finding prompted us to test other frequent amino acid variants in the CypA-binding region and the results revealed MxB-resistant mutations at amino acid positions 86, 87, 88 and 92 in capsid. All these mutations diminished the interaction of HIV-1 capsid with CypA.
  
  
  CONCLUSIONS
  Our results demonstrate the existence of MxB-resistant T/F HIV-1 strains. The high prevalence of MxB-resistant mutations in the CypA-binding loop indicates the significant selective pressure of MxB on HIV-1 replication in vivo especially given that this viral resistance mechanism operates at expense of losing CypA.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Liu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Pan
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Liang
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
mesh_terms: D021984:Cyclophilin A / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D064547:Myxovirus Resistance Proteins / Q000378:metabolism*; D011485:Protein Binding; D012641:Selection, Genetic
chemical_list: D016655:HIV Core Protein p24; C579068:MX2 protein, human; D050505:Mutant Proteins; D064547:Myxovirus Resistance Proteins; D021984:Cyclophilin A