Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection.
Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein that regulates nuclear import of the viral preintegration complex and facilitates infection of nondividing cells, such as macrophages. Studies demonstrated that a fraction of Vpr molecules is phosphorylated in the virions and in HIV-1-infected cells, but the role of phosphorylation in nuclear import activity of Vpr has not been established. We found that Vpr is phosphorylated predominantly on the serine residue in position 79, and mutations affecting Vpr phosphorylation significantly attenuated viral replication in macrophages, but not in activated T lymphocytes or cell lines. The replication defect was mapped by polymerase chain reaction analysis to the step of nuclear import. These results suggest that phosphorylation of Vpr regulates its activity in the nuclear import of the HIV-1 preintegration complex.
Agostini
Isabelle
I
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Popov
Serguei
S
Hao
Tang
T
Li
Jian Hua
JH
Dubrovsky
Larisa
L
Chaika
Oleg
O
Chaika
Nina
N
Lewis
Robert
R
Bukrinsky
Michael
M
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology*; D016336:Gene Products, vpr / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus