HIV-1 myös näytttää kaapanneen myös IP6

• VIRUSES
  
   2018 Nov 15;10(11):640. doi: 10.3390/v10110640.
  

  IP6 Regulation of HIV Capsid Assembly, Stability, and Uncoating

  
  

  
  

  Robert A Dick  ¹ , Donna L Mallery  ² , Volker M Vogt  ³ , Leo C James  ⁴

  PMCID: PMC6267275
  DOI: 10.3390/v10110640
  Free PMC article
  
   Structures of immature EIAV Gag lattices reveal a conserved role for IP6 in lentivirus assembly.
  

  Dick RA, Xu C, Morado DR, Kravchuk V, Ricana CL, Lyddon TD, Broad AM, Feathers JR, Johnson MC, Vogt VM, Perilla JR, Briggs JAG, Schur FKM. PLoS Pathog. 2020 Jan 27;16(1):e1008277. doi: 10.1371/journal.ppat.1008277. eCollection 2020 Jan. PMID: 31986188 Free PMC article.
   
• Inositol phosphates are assembly co-factors for HIV-1.
  

  Dick RA, Zadrozny KK, Xu C, Schur FKM, Lyddon TD, Ricana CL, Wagner JM, Perilla JR, Ganser-Pornillos BK, Johnson MC, Pornillos O, Vogt VM. Nature. 2018 Aug;560(7719):509-512. doi: 10.1038/s41586-018-0396-4. Epub 2018 Aug 1. PMID: 30069050 Free PMC article. Abstract
  

  A short, 14-amino-acid segment called SP1, located in the Gag structural protein¹, has a critical role during the formation of the HIV-1 virus particle. During virus assembly, the SP1 peptide and seven preceding residues fold into a six-helix bundle, which holds together the Gag hexamer and facilitates the formation of a curved immature hexagonal lattice underneath the viral membrane^2,3. Upon completion of assembly and budding, proteolytic cleavage of Gag leads to virus maturation, in which the immature lattice is broken down; the liberated CA domain of Gag then re-assembles into the mature conical capsid that encloses the viral genome and associated enzymes. Folding and proteolysis of the six-helix bundle are crucial rate-limiting steps of both Gag assembly and disassembly, and the six-helix bundle is an established target of HIV-1 inhibitors^4,5. Here, using a combination of structural and functional analyses, we show that inositol hexakisphosphate (InsP6, also known as IP₆) facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP₆ makes ionic contacts with two rings of lysine residues at the centre of the Gag hexamer. Proteolytic cleavage then unmasks an alternative binding site, where IP₆ interaction promotes the assembly of the mature capsid lattice. These studies identify IP₆ as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1.
  
• IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis.
  

  Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC. Elife. 2018 May 31;7:e35335. doi: 10.7554/eLife.35335. PMID: 29848441 Free PMC article Abstract
  

  The HIV capsid is semipermeable and covered in electropositive pores that are essential for viral DNA synthesis and infection. Here, we show that these pores bind the abundant cellular polyanion IP₆, transforming viral stability from minutes to hours and allowing newly synthesised DNA to accumulate inside the capsid. An arginine ring within the pore coordinates IP₆, which strengthens capsid hexamers by almost 10°C. Single molecule measurements demonstrate that this renders native HIV capsids highly stable and protected from spontaneous collapse. Moreover, encapsidated reverse transcription assays reveal that, once stabilised by IP₆, the accumulation of new viral DNA inside the capsid increases >100 fold. Remarkably, isotopic labelling of inositol in virus-producing cells reveals that HIV selectively packages over 300 IP₆ molecules per infectious virion. We propose that HIV recruits IP₆ to regulate capsid stability and uncoating, analogous to picornavirus pocket factors. HIV-1/IP₆/capsid/co-factor/reverse transcription.
  
• Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle.
  

  Novikova M, Zhang Y, Freed EO, Peng K. Version 2. Virol Sin. 2019 Apr;34(2):119-134. doi: 10.1007/s12250-019-00095-3. Epub 2019 Apr 26. PMID: 31028522 Free PMC article. Review.Abstract
  

  Human immunodeficiency virus-1 capsid (HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral pre-integration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.
  
• Revisiting HIV-1 uncoating.
  

  Arhel N. Retrovirology. 2010 Nov 17;7:96. doi: 10.1186/1742-4690-7-96. PMID: 21083892 Free PMC article. Review.

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