PMID- 20554775
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 84
IP  - 17
DP  - 2010 Sep
TI  - Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear 
      import and replication.
PG  - 8650-63
LID - 10.1128/JVI.00508-10 [doi]
AB  - HIV-1 employs the cellular nuclear import machinery to actively transport its 
      preintegration complex (PIC) into the nucleus for integration of the viral DNA. 
      Several viral karyophilic proteins and cellular import factors have been 
      suggested to contribute to HIV-1 PIC nuclear import and replication. However, how 
      HIV interacts with different cellular machineries to ensure efficient nuclear 
      import of its preintegration complex in dividing and nondividing cells is still 
      not fully understood. In this study, we have investigated different importin 
      alpha (Impalpha) family members for their impacts on HIV-1 replication, and we 
      demonstrate that short hairpin RNA (shRNA)-mediated Impalpha3 knockdown (KD) 
      significantly impaired HIV infection in HeLa cells, CD4(+) C8166 T cells, and 
      primary macrophages. Moreover, quantitative real-time PCR analysis revealed that 
      Impalpha3-KD resulted in significantly reduced levels of viral 2-long-terminal 
      repeat (2-LTR) circles but had no effect on HIV reverse transcription. All of 
      these data indicate an important role for Impalpha3 in HIV nuclear import. In an 
      attempt to understand how Impalpha3 participates in HIV nuclear import and 
      replication, we first demonstrated that the HIV-1 karyophilic protein integrase 
      (IN) was able to interact with Impalpha3 both in a 293T cell expression system 
      and in HIV-infected CD4(+) C8166 T cells. Deletion analysis suggested that a 
      region (amino acids [aa] 250 to 270) in the C-terminal domain of IN is involved 
      in this viral-cellular protein interaction. Overall, this study demonstrates for 
      the first time that Impalpha3 is an HIV integrase-interacting cofactor that is 
      required for efficient HIV-1 nuclear import and replication in both dividing and 
      nondividing cells.
FAU - Ao, Zhujun
AU  - Ao Z
AD  - Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, 
      Faculty of Medicine, University of Manitoba, 508-745 William Avenue, Winnipeg R3E 
      0J9, Canada.
FAU - Danappa Jayappa, Kallesh
AU  - Danappa Jayappa K
FAU - Wang, Binchen
AU  - Wang B
FAU - Zheng, Yingfeng
AU  - Zheng Y
FAU - Kung, Sam
AU  - Kung S
FAU - Rassart, Eric
AU  - Rassart E
FAU - Depping, Reinhard
AU  - Depping R
FAU - Kohler, Matthias
AU  - Kohler M
FAU - Cohen, Eric A
AU  - Cohen EA
FAU - Yao, Xiaojian
AU  - Yao X
LA  - eng
GR  - HOP-81180/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100616
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (KPNA4 protein, human)
RN  - 0 (alpha Karyopherins)
RN  - EC 2.7.7.- (HIV Integrase)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Cell Line
MH  - Cell Nucleus/*metabolism
MH  - HIV Infections/genetics/*metabolism/virology
MH  - HIV Integrase/genetics/*metabolism
MH  - HIV-1/*enzymology/genetics/physiology
MH  - HeLa Cells
MH  - Humans
MH  - *Virus Replication
MH  - alpha Karyopherins/genetics/*metabolism
PMC - PMC2919037
EDAT- 2010/06/18 06:00
MHDA- 2010/09/18 06:00
PMCR- 2011/03/01
CRDT- 2010/06/18 06:00
PHST- 2010/06/18 06:00 [entrez]
PHST- 2010/06/18 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - JVI.00508-10 [pii]
AID - 0508-10 [pii]
AID - 10.1128/JVI.00508-10 [doi]
PST - ppublish
SO  - J Virol. 2010 Sep;84(17):8650-63. doi: 10.1128/JVI.00508-10. Epub 2010 Jun 16.