Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells.
Mutants of human immunodeficiency virus type 2 (HIV-2) carrying a frame-shift mutation in vpx, vpr, and in both genes were monitored for their growth potentials in a newly established lymphocytic cell line, HSC-F. Worthy of note, the replication of a vpx single mutant, but not vpr, was severely impaired in these cells, and that of a vpx-vpr double mutant was more damaged. Defective replication sites of the vpx single and vpx-vpr double mutants were demonstrated to be mapped, respectively, to the nuclear import of viral genome, and to both, this process and the virus assembly/release stage. While the mutational effect of vpr was small, the replication efficiency in one cycle of the vpx mutant relative to that of wild-type virus was estimated to be 10%. The growth phenotypes of the vpx, vpr, and vpx-vpr mutant viruses in HSC-F cells were essentially repeated in primary human lymphocytes. In primary human macrophages, whereas the vpx and vpx-vpr mutants did not grow at all, the vpr mutant grew equally as well as the wild-type virus. These results strongly suggested that Vpx is critical for up-regulation of HIV-2 replication in natural target cells by enhancing the genome nuclear import, and that Vpr promotes HIV-2 replication somewhat, at least in lymphocytic cells, at a very late replication phase.
Ueno
Fumiko
F
Department of Ophthalmology and Visual Neuroscience, The University of Tokushima School of Medicine, Tokushima 770-8503, Japan.
Shiota
Hiroshi
H
Miyaura
Maki
M
Yoshida
Akiko
A
Sakurai
Akiko
A
Tatsuki
Junko
J
Koyama
A Hajime
AH
Akari
Hirofumi
H
Adachi
Akio
A
Fujita
Mikako
M
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D016368:Frameshift Mutation; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D016334:Genes, vpr; D015498:HIV-2 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D016336:Gene Products, vpr; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus