PMID- 25568209
OWN - NLM
STAT- MEDLINE
DCOM- 20150521
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 7
DP  - 2015 Apr
TI  - Human immunodeficiency virus type 1 employs the cellular dynein light chain 1 
      protein for reverse transcription through interaction with its integrase protein.
PG  - 3497-511
LID - 10.1128/JVI.03347-14 [doi]
AB  - In this study, we examined the requirement for host dynein adapter proteins such 
      as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and 
      p150(Glued) in early steps of human immunodeficiency virus type 1 (HIV-1) 
      replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or 
      p150(Glued), resulted in significantly lower levels of HIV-1 reverse 
      transcription in cells. Following an attempt to determine how DYNLL1 could impact 
      HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 
      integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase 
      (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction 
      motifs in IN, we identified the motifs (52)GQVD and (250)VIQD in IN as essential 
      for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 
      (HIV-1IN(Q53A/Q252A)) exhibited impaired reverse transcription. Through further 
      investigations, we have also detected relatively smaller amounts of particulate 
      CA in DYNLL1-KD cells or in infections with HIV-1IN(Q53A/Q252A) mutant virus. 
      Overall, our study demonstrates the novel interaction between HIV-1 IN and 
      cellular DYNLL1 proteins and suggests the requirement of this virus-cell 
      interaction for proper uncoating and efficient reverse transcription of HIV-1. 
      IMPORTANCE: Host cellular DYNLL1, DYNLT1, and p150(Glued) proteins have been 
      implicated in the replication of several viruses. However, their roles in HIV-1 
      replication have not been investigated. For the first time, we demonstrated that 
      during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was 
      found to have a role in proper uncoating and efficient reverse transcription of 
      HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future 
      anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN 
      in HIV-1 uncoating and reverse transcription, it also predicts a possible 
      mechanism by which IN contributes to these early viral replication steps.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Jayappa, Kallesh Danappa
AU  - Jayappa KD
AD  - Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, 
      Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
FAU - Ao, Zhujun
AU  - Ao Z
AD  - Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, 
      Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
FAU - Wang, Xiaoxia
AU  - Wang X
AD  - Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, 
      Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
FAU - Mouland, Andrew J
AU  - Mouland AJ
AD  - HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General 
      Hospital and McGill University, Montreal, Quebec, Canada.
FAU - Shekhar, Sudhanshu
AU  - Shekhar S
AD  - Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, 
      Canada.
FAU - Yang, Xi
AU  - Yang X
AD  - Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, 
      Canada.
FAU - Yao, Xiaojian
AU  - Yao X
AD  - Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, 
      Faculty of Medicine, University of Manitoba, Winnipeg, Canada 
      yao2@cc.umanitoba.ca.
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150107
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DCTN1 protein, human)
RN  - 0 (DYNLT1 protein, human)
RN  - 0 (Dynactin Complex)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 2.7.7.- (HIV Integrase)
RN  - EC 3.6.1.- (DYNLL1 protein, human)
RN  - EC 3.6.4.2 (Cytoplasmic Dyneins)
RN  - EC 3.6.4.2 (Dyneins)
SB  - IM
MH  - Amino Acid Motifs
MH  - Cell Line
MH  - Cytoplasmic Dyneins/*metabolism
MH  - DNA Mutational Analysis
MH  - Dynactin Complex
MH  - Dyneins/metabolism
MH  - Gene Knockdown Techniques
MH  - HIV Integrase/genetics/*metabolism
MH  - HIV-1/genetics/*physiology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Microtubule-Associated Proteins/metabolism
MH  - *Reverse Transcription
MH  - *Virus Uncoating
PMC - PMC4403391
EDAT- 2015/01/09 06:00
MHDA- 2015/05/23 06:00
PMCR- 2015/10/01
CRDT- 2015/01/09 06:00
PHST- 2015/01/09 06:00 [entrez]
PHST- 2015/01/09 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - JVI.03347-14 [pii]
AID - 03347-14 [pii]
AID - 10.1128/JVI.03347-14 [doi]
PST - ppublish
SO  - J Virol. 2015 Apr;89(7):3497-511. doi: 10.1128/JVI.03347-14. Epub 2015 Jan 7.