title: Re-visiting the functional Relevance of the highly conserved Serine 40 Residue within HIV-1 p6(Gag).
abstract: BACKGROUND
  HIV-1 formation is driven by the viral structural polyprotein Gag, which assembles at the plasma membrane into a hexagonal lattice. The C-terminal p6(Gag) domain harbors short peptide motifs, called late domains, which recruit the cellular endosomal sorting complex required for transport and promote HIV-1 abscission from the plasma membrane. Similar to late domain containing proteins of other viruses, HIV-1 p6 is phosphorylated at multiple residues, including a highly conserved serine at position 40. Previously published studies showed that an S40F exchange in p6(Gag) severely affected virus infectivity, while we had reported that mutation of all phosphorylatable residues in p6(Gag) had only minor effects.
  
  
  RESULTS
  We introduced mutations into p6(Gag) without affecting the overlapping pol reading frame by using an HIV-1 derivative where gag and pol are genetically uncoupled. HIV-1 derivatives with a conservative S40N or a non-conservative S40F exchange were produced. The S40F substitution severely affected virus maturation and infectivity as reported before, while the S40N exchange caused no functional defects and the variant was fully infectious in T-cell lines and primary T-cells.
  
  
  CONCLUSIONS
  An HIV-1 variant carrying a conservative S40N exchange in p6(Gag) is fully functional in tissue culture demonstrating that neither S40 nor its phosphorylation are required for HIV-1 release and maturation. The phenotype of the S40F mutation appears to be caused by the bulky hydrophobic residue introduced into a flexible region.
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, D-69120, Heidelberg, Germany. Benjamin.Radestock@med.uni-heidelberg.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Radestock
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, D-69120, Heidelberg, Germany. Robin.Burk@med.uni-heidelberg.de.
authors.forename: Robin
authors.initials: R
authors.lastname: Burk
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, D-69120, Heidelberg, Germany. Barbara.Mueller@med.uni-heidelberg.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, D-69120, Heidelberg, Germany. Hans-Georg.Kraeusslich@med.uni-heidelberg.de.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
mesh_terms: D019943:Amino Acid Substitution; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1; D012694:Serine