Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication
Abstract 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 integrati...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-04-01
|
Series: | Retrovirology |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12977-019-0474-1 |
id |
doaj-883e6762385b47b5b4bfb5e0dfb1fb41 |
---|---|
record_format |
Article |
spelling |
doaj-883e6762385b47b5b4bfb5e0dfb1fb412020-11-25T02:00:29ZengBMCRetrovirology1742-46902019-04-0116111810.1186/s12977-019-0474-1Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replicationPooja Yadav0Souvik Sur1Dipen Desai2Smita Kulkarni3Vartika Sharma4Vibha Tandon5Department of Chemistry, University of DelhiSpecial Center for Molecular Medicine, Jawaharlal Nehru UniversityNational AIDS Research InstituteNational AIDS Research InstituteInternational Centre for Genetics Engineering and BiotechnologySpecial Center for Molecular Medicine, Jawaharlal Nehru UniversityAbstract 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.http://link.springer.com/article/10.1186/s12977-019-0474-1PSFHIVHIV-1 integraseHost–pathogen interaction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pooja Yadav Souvik Sur Dipen Desai Smita Kulkarni Vartika Sharma Vibha Tandon |
spellingShingle |
Pooja Yadav Souvik Sur Dipen Desai Smita Kulkarni Vartika Sharma Vibha Tandon Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication Retrovirology PSF HIV HIV-1 integrase Host–pathogen interaction |
author_facet |
Pooja Yadav Souvik Sur Dipen Desai Smita Kulkarni Vartika Sharma Vibha Tandon |
author_sort |
Pooja Yadav |
title |
Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication |
title_short |
Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication |
title_full |
Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication |
title_fullStr |
Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication |
title_full_unstemmed |
Interaction of HIV-1 integrase with polypyrimidine tract binding protein and associated splicing factor (PSF) and its impact on HIV-1 replication |
title_sort |
interaction of hiv-1 integrase with polypyrimidine tract binding protein and associated splicing factor (psf) and its impact on hiv-1 replication |
publisher |
BMC |
series |
Retrovirology |
issn |
1742-4690 |
publishDate |
2019-04-01 |
description |
Abstract 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. |
topic |
PSF HIV HIV-1 integrase Host–pathogen interaction |
url |
http://link.springer.com/article/10.1186/s12977-019-0474-1 |
work_keys_str_mv |
AT poojayadav interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication AT souviksur interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication AT dipendesai interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication AT smitakulkarni interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication AT vartikasharma interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication AT vibhatandon interactionofhiv1integrasewithpolypyrimidinetractbindingproteinandassociatedsplicingfactorpsfanditsimpactonhiv1replication |
_version_ |
1724960240812687360 |