Tion in both HEK293 cells and THP-1-derived macrophages. The effectTion in both HEK293 cells and

Tion in both HEK293 cells and THP-1-derived macrophages. The effect
Tion in both HEK293 cells and THP-1-derived macrophages. The effect of TRIM11 on uncoating is dependent on microtubule dynamics, whereas independent of proteasomal or lysosomal pathway. All of these findings support the restriction of HIV-1 transduction by TRIM11, while MLV transduction is not influenced by TRIM11. The PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26577270 HIV-1 CA mutant G89V is insensitive to the effect of TRIM11, which strengthened the possibility that the capsid of HIV-1 could be the determinant for restriction by TRIM11. Thus, our work presents the first human TRIM family member that recognizes HIV-1 capsid and accelerates its uncoating. Multiple HIV-1 capsid binding proteins have been identified [15, 16, 25, 27?0], most of which, like CSPF6, NUP153, NUP358, TNPO3 and CypA, were shown as dependency factors for HIV-1 replication [25, 28?0]. These factors aid properly uncoating of HIV-1 capsid or escorting viral DNA into nucleus. In the other side, some capsid-binding proteins could perturb uncoating and impede HIV-1 replication. MxB was identified as an IFN- inducible restriction factor that could block viral DNA nuclear entry by interacting with HIV-1 capsid to increase its stability [16]. In this study, we introduced TRIM11 as a new HIV-1 capsid binding factor that will tilt the balance of uncoating process in favor of accelerating when it is overexpressed in cells, which will result in reduced viral reverse transcription levels. TRIM11 is not the only human TRIM family member that could associate with HIV-1 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25609842 capsid. TRIM6 and TRIM34, which are closely related to TRIM5 in sequence similarity, have been reported to bind in vitro assembled HIV-1 capsid, but they do not have the ability to restrict HIV-1 replication [20]. By analysis of extensive TRIM5rh mutants, Yang et al., demonstrated that binding to HIV-1 capsid is necessary, but not sufficient, for HIV-1 restriction [31]. Cytoplasmic body formation and E3 ubiquitin ligase activity were also implicated in TRIM5rh-mediated capsid disruption and restriction of reverse transcription [32?4]. The restriction activity of TRIM5 was recently reported to correlate with its ability to induce TAK-1 dependent innate immune signaling [35]. Thus, in addition to binding with capsid, some domains of TRIM5rh must function in a cryptic mechanism to accelerate viral capsid uncoating. In accordance to these findings, the chimeric proteins TRIM-CypA and Trim-NUP153(C), which use different domain for binding to capsid, sustain the restriction ability of TRIM5rhYuan et al. Retrovirology (2016) 13:Page 10 ofFig. 6 TRIM11 restricts HIV-1 early stage of replication in THP-1 cells. a, b THP-1 cells expressing TRIM11-HA or empty vector pCDH were treated with 100 nM PMA for 48 h followed by infection with indicated amounts of HIV-1 and viral transduction was analyzed by luciferase activity at 48 h post infection (a), and late reverse transcripts were measured by qPCR (b). c The indicated THP-1 cell lines were treated with 100 nM PMA for 48 h followed by infection with HIV-1 for 1 h. Cell lysates were processed for the fate-of-capsid assay as described in Fig. 2c. The LDN193189 cancer levels of p24 in pelletable and input fractions were measured by densitometry and pellet/input ratio was calculated. c Similar experiments were carried out as described in a , with THP-1 cells in which TRIM11 expression levels were stably knocked down with shRNA-1 specific to TRIM11. Error bars represent the standard deviations from three independent replicates. *P < 0.[36?8]. Th.