Showing papers by "Jun Komano published in 2008"
Yokohama City University1, Kitasato University2, Tokyo Medical and Dental University3, Beaumont Hospital4, National Institutes of Health5, Tokyo University of Science6, National Defense Medical College7, Royal College of Surgeons in Ireland8, Boston Children's Hospital9, Kyushu University10, Ehime University11
TL;DR: The results indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.
Abstract: Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.
79 citations
TL;DR: The data suggest that CX CR4 trafficking can be modified in terms of its recruitment to the plasma membrane without enhancing the degradation or arresting vesicular transport of CXCR4.
Abstract: We have discovered that an N-terminal deletion mutant of a membrane protein, CD63, (CD63DeltaN) blocks entry of CXCR4-using, T-cell tropic human immunodeficiency virus type 1 (X4 HIV-1) by suppressing CXCR4 surface expression. This suppression was observed for CXCR4 but not for CD4, CCR5, CD25, CD71 or other tetraspanin proteins. The suppression of CXCR4 expression on the plasma membrane appeared to be caused by mislocalization of CXCR4 and exclusive transportation of CXCR4 toward intracellular organelles, mainly late endosomes/lysosomes. Our data suggest that CXCR4 trafficking can be modified in terms of its recruitment to the plasma membrane without enhancing the degradation or arresting vesicular transport of CXCR4.
60 citations
TL;DR: This study replaced the myristoylation signal of MA with a well-studied phosphatidylinositol 4,5-biphosphate-binding plasma membrane (PM) targeting motif, the phospholipase C-δ1 pleckstrin homology (PH) domain, and demonstrated infectious pseudovirion production without myristoyslated Pr55Gag.
Abstract: The matrix domain (MA) of human immunodeficiency virus type 1 Pr55Gag is covalently modified with a myristoyl group that mediates efficient viral production. However, the role of myristoylation, particularly in the viral entry process, remains uninvestigated. This study replaced the myristoylation signal of MA with a well-studied phosphatidylinositol 4,5-biphosphate-binding plasma membrane (PM) targeting motif, the phospholipase C-δ1 pleckstrin homology (PH) domain. PH–Gag–Pol PM targeting and viral production efficiencies were improved compared with Gag–Pol, consistent with the estimated increases in Gag–PM affinity. Both virions were recovered in similar sucrose density-gradient fractions and had similar mature virion morphologies. Importantly, PH–Gag–Pol and Gag–Pol pseudovirions had almost identical infectivity, suggesting a dispensable role for myristoylation in the virus life cycle. PH–Gag–Pol might be useful in separating the myristoylation-dependent processes from the myristoylation-independent processes. This the first report demonstrating infectious pseudovirion production without myristoylated Pr55Gag.
23 citations
TL;DR: This work provides direct experimental data demonstrating that Brd4‐CTD serves as a specific inhibitor of HIV‐1 replication in T cells, suggesting that this method is a powerful tool for the identification of host factors that regulate HIV‐ 1 replication inT cells.
19 citations
TL;DR: It is demonstrated that cyclin K/CPR4-containing positive transcription elongation factor b complexes are unresponsive to Tat and HEXIM1-mediated inactivation and functions as a natural inhibitor of primate lentiviruses.
Abstract: The positive transcription elongation factor b complexes comprise CDK9 and a C-type cyclin, required for the efficient expression of both eukaryotic and primate lentivirus-encoded genes Cyclin K/CPR4 is the least studied of the positive transcription elongation factor b-forming cyclins Here, we demonstrate that cyclin K/CPR4-containing positive transcription elongation factor b complexes are unresponsive to Tat and HEXIM1-mediated inactivation Enhancing expression of cyclin K/CPR4 inhibited the human and simian immunodeficiency viral replication These data indicate that cyclin K/CPR4 functions as a natural inhibitor of primate lentiviruses
6 citations