Hisashi Akiyama, PhD

Assistant Professor, Boston University Chobanian & Avedisian School of Medicine

Biography

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.

Publications

  • Published 9/8/2025

    Jalloh S, Hughes IK, Akiyama H, Gojanovich AD, Quiñones-Molina AA, Yang M, Henderson AJ, Mostoslavsky G, Gummuluru S. Expression of intron-containing HIV-1 RNA induces NLRP1 inflammasome activation in myeloid cells. PLoS Biol. 2025 Sep; 23(9):e3003320. PMID: 40920844.

    Read at: PubMed

  • Published 8/25/2025

    Hughes IK, Kharytonchyk S, Ramaswamy S, Jalloh S, Hood JB, He X, Henderson AJ, Akiyama H, Telesnitsky A, Gummuluru S. 5' cap sequestration is required for sensing of unspliced HIV-1 RNA by MDA5. bioRxiv. 2025 Aug 25. PMID: 40909469.

    Read at: PubMed

  • Published 6/10/2025

    Ramaswamy S, Akiyama H, Berrigan J, Quiñones-Molina AA, Olson AJ, Chen Y, Liang Y, Henderson AJ, Asundi A, Sagar M, Gummuluru S. The macrophage-intrinsic MDA5/IRF5 axis drives HIV-1 intron-containing RNA-induced inflammatory responses. J Clin Invest. 2025 Aug 15; 135(16). PMID: 40493408.

    Read at: PubMed

  • Published 5/19/2025

    Hughes IK, Hood JB, Quiñones-Molina AA, Akiyama H, Gummuluru S. Evasion of CARD8 Activation During HIV-1 Assembly. bioRxiv. 2025 May 19. PMID: 40475532.

    Read at: PubMed

  • Published 11/1/2023

    Komori M, Morey AL, Quiñones-Molina AA, Fofana J, Romero L, Peters E, Matsuda K, Gummuluru S, Smith JF, Akahata W, Akiyama H. Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine. bioRxiv. 2023 Nov 01. PMID: 37961509.

    Read at: PubMed

Education

  • Kyoto University, PhD
  • Kyoto University, BE/BEng