Proline 35 of human immunodeficiency virus type 1 (HIV-1) Vpr regulates the integrity of the N-terminal helix and the incorporation of Vpr into virus particles and supports the replication of R5-tropic HIV-1 in human lymphoid tissue ex vivo.
Mutational analysis of the four conserved proline residues in human immunodeficiency virus type 1 (HIV-1) Vpr reveals that only Pro-35 is required for efficient replication of R5-tropic, but not of X4-tropic, viruses in human lymphoid tissue (HLT) cultivated ex vivo. While Vpr-mediated apoptosis and G(2) cell cycle arrest, as well as the expression and subcellular localization of Vpr, were independent, the capacity for encapsidation of Vpr into budding virions was dependent on Pro-35. (1)H nuclear magnetic resonance data suggest that mutation of Pro-35 causes a conformational change in the hydrophobic core of the molecule, whose integrity is required for the encapsidation of Vpr, and thus, Pro-35 supports the replication of R5-tropic HIV-1 in HLT.
Votteler
Jörg
J
Institute of Virology, University of Erlangen-Nuremberg, Erlangen, Germany.
Studtrucker
Nicole
N
Sörgel
Stefan
S
Münch
Jan
J
Rücker
Elke
E
Kirchhoff
Frank
F
Schick
Bernhard
B
Henklein
Peter
P
Fossen
Torgils
T
Bruns
Karsten
K
Sharma
Alok
A
Wray
Victor
V
Schubert
Ulrich
U
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016336:Gene Products, vpr / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D008221:Lymphoid Tissue / Q000821:virology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011392:Proline; D017433:Protein Structure, Secondary / Q000235:genetics*; D019065:Virus Assembly / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011392:Proline