Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins.
The three-dimensional (3-D) structure of human immunodeficiency virus type 2 (HIV-2) Vpr/Vpx was predicted by homology modeling based on the NMR structure of human immunodeficiency virus type 1 (HIV-1) Vpr. The three proteins similarly have three major amphipathic alpha-helices. In contrast to HIV-1 Vpr, Vpr/Vpx of HIV-2 have a long N-terminal loop and clustered prolines in the second half of the C-terminal loop. HIV-2 Vpx uniquely contains a long region between the second and third major helices, and bears several glycines in the first half of the C-terminal loop. Instead of the glycines, there is a group of hydrophilic amino acids and arginines in the corresponding regions of the two Vprs. To compare the cytopathogenic potentials of HIV-1 Vpr and HIV-2 Vpr/Vpx, we examined the production of luciferase as a marker of cell damage. We further analyzed the characteristics of cells transduced with vpr/vpx genes driven by an inducible promoter. The results obtained clearly show that structurally similar, but distinct, HIV Vpr/Vpx proteins are detrimental to target cells.
Khamsri
Boonruang
B
Department of Virology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Murao
Fumiko
F
Yoshida
Akiko
A
Sakurai
Akiko
A
Uchiyama
Tsuneo
T
Shirai
Hiroki
H
Matsuo
Yo
Y
Fujita
Mikako
M
Adachi
Akio
A
D000595:Amino Acid Sequence; D003588:Cytopathogenic Effect, Viral / Q000502:physiology*; D005786:Gene Expression Regulation; D016336:Gene Products, vpr / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000472:pathogenicity; D015498:HIV-2 / Q000737:chemistry / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus