PMID- 31036027
OWN - NLM
STAT- MEDLINE
DCOM- 20190718
LR  - 20200225
IS  - 1742-4690 (Electronic)
IS  - 1742-4690 (Linking)
VI  - 16
IP  - 1
DP  - 2019 Apr 29
TI  - Interaction of HIV-1 integrase with polypyrimidine tract binding protein and 
      associated splicing factor (PSF) and its impact on HIV-1 replication.
PG  - 12
LID - 10.1186/s12977-019-0474-1 [doi]
LID - 12
AB  - BACKGROUND: The different interactions between viral proteins and cellular host 
      proteins are required for efficient replication of HIV-1. Various reports 
      implicated host cellular proteins as a key factor that either interact directly 
      with HIV-1 integrase (IN) or get involved in the integration process of virus 
      resulting in the modulation of integration step. Polypyrimidine tract binding 
      protein and associated splicing factor (PSF) has diverse functions inside the 
      cell such as transcriptional regulation, DNA repair, acts as nucleic acids 
      binding protein and regulate replication and infectivity of different viruses. 
      RESULTS: The protein binding study identified the association of host protein PSF 
      with HIV-1 integrase. The siRNA knockdown (KD) of PSF resulted in increased viral 
      replication in TZM-bl cells, suggesting PSF has negative influence on viral 
      replication. The quantitative PCR of virus infected PSF knockdown TZM-bl cells 
      showed more integrated DNA and viral cDNA as compared to control cells. We did 
      not observe any significant difference between the amount of early reverse 
      transcription products as well as infectivity of virus in the PSF KD and control 
      TZM-bl cells. Molecular docking study supported the argument that PSF hinders the 
      binding of viral DNA with IN. CONCLUSION: In an attempt to study the host 
      interacting protein of IN, we have identified a new interacting host protein PSF 
      which is a splicing factor and elucidated its role in integration and viral 
      replication. Experimental as well as in silico analysis inferred that the host 
      protein causes not only change in the integration events but also targets the 
      incoming viral DNA or the integrase-viral DNA complex. The role of PSF was also 
      investigated at early reverse transcript production as well as late stages. The 
      PSF is causing changes in integration events, but it does not over all make any 
      changes in the virus infectivity. MD trajectory analyses provided a strong clue 
      of destabilization of Integrase-viral DNA complex occurred due to PSF interaction 
      with the conserved bases of viral DNA ends that are extremely crucial contact 
      points with integrase and indispensable for integration. Thus our study 
      emphasizes the negative influence of PSF on HIV-1 replication.
FAU - Yadav, Pooja
AU  - Yadav P
AD  - Department of Chemistry, University of Delhi, Delhi, 110007, India.
FAU - Sur, Souvik
AU  - Sur S
AD  - Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 
      110067, India.
FAU - Desai, Dipen
AU  - Desai D
AD  - National AIDS Research Institute, Pune, Maharashtra, 411026, India.
FAU - Kulkarni, Smita
AU  - Kulkarni S
AD  - National AIDS Research Institute, Pune, Maharashtra, 411026, India.
FAU - Sharma, Vartika
AU  - Sharma V
AD  - International Centre for Genetics Engineering and Biotechnology, New Delhi, 
      110067, India.
FAU - Tandon, Vibha
AU  - Tandon V
AD  - Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 
      110067, India. vtandon@mail.jnu.ac.in.
LA  - eng
GR  - project id 38/UPE-II/International
GR  - -/DST-Purse/International
GR  - Seed/DISHA/WOSB/009/2012/WOS-B/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190429
PL  - England
TA  - Retrovirology
JT  - Retrovirology
JID - 101216893
RN  - 0 (DNA, Viral)
RN  - 0 (RNA Splicing Factors)
RN  - 0 (RNA, Small Interfering)
RN  - 139076-35-0 (Polypyrimidine Tract-Binding Protein)
RN  - EC 2.7.7.- (HIV Integrase)
RN  - YY6481J2FF (p31 integrase protein, Human immunodeficiency virus 1)
SB  - IM
MH  - DNA, Viral/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - HIV Integrase/genetics/*metabolism
MH  - HIV-1/physiology
MH  - *Host Microbial Interactions
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Polypyrimidine Tract-Binding Protein/genetics/*metabolism
MH  - Protein Binding
MH  - RNA Splicing
MH  - RNA Splicing Factors/genetics/*metabolism
MH  - RNA, Small Interfering
MH  - Reverse Transcription
MH  - Virus Integration
MH  - *Virus Replication
PMC - PMC6489298
OTO - NOTNLM
OT  - HIV
OT  - HIV-1 integrase
OT  - Host-pathogen interaction
OT  - PSF
COIS- The authors declare that they have no competing interests.
EDAT- 2019/05/01 06:00
MHDA- 2019/07/19 06:00
PMCR- 2019/04/29
CRDT- 2019/05/01 06:00
PHST- 2018/11/22 00:00 [received]
PHST- 2019/04/11 00:00 [accepted]
PHST- 2019/05/01 06:00 [entrez]
PHST- 2019/05/01 06:00 [pubmed]
PHST- 2019/07/19 06:00 [medline]
PHST- 2019/04/29 00:00 [pmc-release]
AID - 10.1186/s12977-019-0474-1 [pii]
AID - 474 [pii]
AID - 10.1186/s12977-019-0474-1 [doi]
PST - epublish
SO  - Retrovirology. 2019 Apr 29;16(1):12. doi: 10.1186/s12977-019-0474-1.