Human immunodeficiency virus type 1 employs the cellular dynein light chain 1 protein for reverse transcription through interaction with its integrase protein. 2015

Kallesh Danappa Jayappa, and Zhujun Ao, and Xiaoxia Wang, and Andrew J Mouland, and Sudhanshu Shekhar, and Xi Yang, and Xiaojian Yao
Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

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. OBJECTIVE 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.

UI MeSH Term Description Entries
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D004398 Dyneins A family of multi-subunit cytoskeletal motor proteins that use the energy of ATP hydrolysis, generated by a ring of AAA ATPASES in the dynein heavy chain, to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria. ATPase, Dynein,Adenosinetriphosphatase, Dynein,Dynein,Dynein ATPase,Dynein Adenosinetriphosphatase,Dynein Heavy Chain,Dynein Intermediate Chain,Dynein Light Chain,Dynein Light Intermediate Chain,Adenosine Triphosphatase, Dynein,Dynein Heavy Chains,Dynein Intermediate Chains,Dynein Light Chains,Dynein Light Intermediate Chains,Chain, Dynein Heavy,Chain, Dynein Intermediate,Chain, Dynein Light,Chains, Dynein Heavy,Chains, Dynein Intermediate,Chains, Dynein Light,Dynein Adenosine Triphosphatase,Heavy Chain, Dynein,Heavy Chains, Dynein,Intermediate Chain, Dynein,Intermediate Chains, Dynein,Light Chain, Dynein,Light Chains, Dynein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072159 Dynactin Complex A multi-subunit protein of EUKARYOTIC CELLS. It functions in bidirectional intracellular transport of ORGANELLES and CYTOPLASMIC VESICLES by linking them to DYNEIN and KINESIN. 150 kDa Dynein-Associated Protein,Dynactin,Dynactin 1,Dynactin Subunit 1,Dynactin Subunit 2,Dynactin Subunit 3,Dynactin Subunit 4,Dynactin-2,Dynactin-3,Dynactin-4,Dynactins,Dynamitin Protein,Dynein Activator Protein,Dynein-Associated Protein, 150-kDa,p150(Glued),p22 Dynactin Light Chain,p50 Dynamitin,150 kDa Dynein Associated Protein,150-kDa Dynein-Associated Protein,Dynactin 2,Dynactin 3,Dynactin 4,Dynamitin, p50,Dynein Associated Protein, 150 kDa
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D048348 Reverse Transcription The biosynthesis of DNA carried out on a template of RNA. Transcription, Reverse
D054884 Host-Pathogen Interactions The interactions between a host and a pathogen, usually resulting in disease. Host Pathogen Interaction,Host-Pathogen Relations,Pathogen-Host Interaction,Pathogen-Host Interactions,Host Pathogen Interactions,Host Pathogen Relations,Host-Pathogen Interaction,Host-Pathogen Relation,Interaction, Host Pathogen,Interaction, Host-Pathogen,Interaction, Pathogen-Host,Interactions, Host Pathogen,Interactions, Host-Pathogen,Interactions, Pathogen-Host,Pathogen Host Interaction,Pathogen Host Interactions,Pathogen Interaction, Host,Pathogen Interactions, Host,Relation, Host-Pathogen,Relations, Host-Pathogen
D055785 Gene Knockdown Techniques The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES. Gene Knock Down Techniques,Gene Knock Down,Gene Knock-Down,Gene Knock-Down Techniques,Gene Knockdown,Gene Knock Downs,Gene Knock-Down Technique,Gene Knock-Downs,Gene Knockdown Technique,Gene Knockdowns,Knock Down, Gene,Knock Downs, Gene,Knock-Down Technique, Gene,Knock-Down Techniques, Gene,Knock-Down, Gene,Knock-Downs, Gene,Knockdown Technique, Gene,Knockdown Techniques, Gene,Knockdown, Gene,Knockdowns, Gene,Technique, Gene Knock-Down,Technique, Gene Knockdown,Techniques, Gene Knock-Down,Techniques, Gene Knockdown

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