title: Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection.
abstract: BACKGROUND
  Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5α restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5α splice variant TRIM5δ in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction.
  
  
  RESULTS
  We show that the interaction of BTBD1 and BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM producer cells. Additionally, interference with the expression of BTBD2 in AGM and human 293T target cells increased their permissiveness to HIV-1 infection two- to three-fold.
  
  
  CONCLUSIONS
  These results do not exclude the possibility that BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in cytoplasmic bodies.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Khurana
authors.forename: Lei
authors.initials: L
authors.lastname: Zhuang
authors.forename: Prasun K
authors.initials: PK
authors.lastname: Moitra
authors.forename: Tzanko S
authors.initials: TS
authors.lastname: Stantchev
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Cutler
authors.forename: Peter
authors.initials: P
authors.lastname: D'Arpa
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D058507:Host Specificity; D006801:Humans; D008958:Models, Molecular; D025941:Protein Interaction Mapping; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C429757:BTBD1 protein, human; C477345:BTBD2 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human