HIV-1 infection requires a functional integrase NLS.
HIV-1 is able to infect nondividing cells productively in part because the postentry viral nucleoprotein complexes are actively imported into the nucleus. In this manuscript, we identify a novel nuclear localization signal (NLS) in the viral integrase (IN) protein that is essential for virus replication in both dividing and nondividing cells. The IN NLS stimulates the efficient nuclear accumulation of viral DNA as well as virion-derived IN protein during the initial stages of infection but is dispensable for catalytic function. Because this NLS is required for infection irrespective of target cell proliferation, we suggest that interactions between uncoated viral nucleoprotein complexes and the host cell nuclear import machinery are critical for HIV-1 infection of all cells.
Bouyac-Bertoia
M
M
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Dvorin
J D
JD
Fouchier
R A
RA
Jenkins
Y
Y
Meyer
B E
BE
Wu
L I
LI
Emerman
M
M
Malim
M H
MH
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D015658:HIV Infections / Q000201:enzymology*; D019427:HIV Integrase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000737:chemistry; D013601:T-Lymphocytes / Q000821:virology
D004279:DNA, Viral; D019913:Nuclear Localization Signals; D019427:HIV Integrase