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Research Expertise & Professional Interests My research goal is to understand pathogenesis of HIV. In particular, I am interested in the role of myeloid cells in establishment and dissemination of HIV infection and mechanisms of virus evasion from innate and adaptive host immune responses. Cells of myeloid lineage such as monocytes, dendritic cells (DCs) and macrophages in addition to CD4+ T cells, are susceptible to HIV infection. Myeloid cells have been shown to play a critical role in HIV acquisition at mucosal surfaces and replication in tissues such as central nervous system. Moreover, tissue-resident macrophages can be a major source of HIV production at the late stages of viral infection. To fully understand HIV pathogenesis, it is crucial to elucidate the roles of myeloid cells in HIV infection. HIV-1 has exploited DCs as a vehicle to infect T cells via a unique mechanism called trans-infection. Our previous work has identified CD169/Siglec1 as the receptor on DCs that binds to virion-incorporated lipids to initiate trans-infection. CD169 not only enhances HIV-1 replication by trans-infecting T cells, but also contributes to immune evasion. Upon binding to HIV-1 particles, CD169 traffics HIV-1 virions into a sac-like plasma membrane-associated structure, which serves as a sanctuary for HIV-1 against neutralizing antibodies. Ongoing projects are focused on a role of CD169–HIV-1 interaction in attenuating host countermeasures against HIV-1 infection including humoral immunity and type I interferon responses. Myeloid cells are sentinel cells and elicit robust immune responses upon sensing of invading pathogens. Since antigen persists chronically in HIV-1 infection, continuous activation of/by myeloid cells may play a key role in chronic immune activation, a hallmark of HIV-1 infection. In fact, it has been shown that infection of macrophages with HIV-1 induces production of pro-inflammatory cytokines and interferon stimulated genes (ISGs) expression. However, the molecular mechanisms underlying the HIV-1-induced activation of macrophages still remain unclear. Current studies are focused on understanding the viral and host factors involved in macrophage activation and its consequences in HIV-1 pathogenesis.

One or more keywords matched the following items that are connected to Akiyama, Hisashi

Item TypeName
Concept HIV Antibodies
Concept HIV-1
Concept HIV-2
Concept HIV Infections
Concept HIV Envelope Protein gp120
Concept HIV Protease
Concept HIV Protease Inhibitors
Concept HIV Integrase
Concept gag Gene Products, Human Immunodeficiency Virus
Concept HIV Reverse Transcriptase
Concept vpr Gene Products, Human Immunodeficiency Virus
Academic Article Transmembrane domain membrane proximal external region but not surface unit-directed broadly neutralizing HIV-1 antibodies can restrict dendritic cell-mediated HIV-1 trans-infection.
Academic Article Interleukin 2-inducible T cell kinase (ITK) facilitates efficient egress of HIV-1 by coordinating Gag distribution and actin organization.
Academic Article Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169.
Academic Article DNA vaccination of macaques by a full-genome simian/human immunodeficiency virus type 1 plasmid chimera that produces non-infectious virus particles.
Academic Article Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type 1.
Academic Article Construction of a novel SHIV having an HIV-1-derived protease gene and its infection to rhesus macaques: a useful tool for in vivo efficacy tests of protease inhibitors.
Academic Article Construction and infection of a new simian/human immunodeficiency chimeric virus (SHIV) containing the integrase gene of the human immunodeficiency virus type 1 genome and analysis of its adaptation to monkey cells.
Academic Article HIV-1 Gag processing intermediates trans-dominantly interfere with HIV-1 infectivity.
Academic Article Probing HIV-1 membrane liquid order by Laurdan staining reveals producer cell-dependent differences.
Academic Article Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells.
Academic Article Virus particle release from glycosphingolipid-enriched microdomains is essential for dendritic cell-mediated capture and transfer of HIV-1 and henipavirus.
Academic Article Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse.
Academic Article CD169-dependent cell-associated HIV-1 transmission: a driver of virus dissemination.
Academic Article CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies.
Academic Article Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated.
Academic Article Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells.
Academic Article Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon.
Academic Article Membrane Fluidity Sensing on the Single Virus Particle Level with Plasmonic Nanoparticle Transducers.
Academic Article HIV-1 replicates and persists in vaginal epithelial dendritic cells.
Academic Article HIV-1 intron-containing RNA expression induces innate immune activation and T cell dysfunction.
Academic Article HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages.
Academic Article Stiffness of HIV-1 Mimicking Polymer Nanoparticles Modulates Ganglioside-Mediated Cellular Uptake and Trafficking.

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  • HIV
  • pathogenesis