Hisashi Akiyama
Research Assistant Professor
Boston University Chobanian & Avedisian School of Medicine
Virology, Immunology & Microbiology

PhD, Kyoto University
BE/BEng, Kyoto University



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.


RNA modification and innate immune activation in HIV infection
07/08/2024 - 06/30/2029 (PI)
NIH/National Institute of Allergy & Infectious Diseases
1R01AI183400-01

Innate immune activation induced by RNA-based vaccines
02/01/2022 - 03/31/2025 (PI)
VLP Therapeutics, Inc.


Innate sensing of HIV in microglia
07/15/2021 - 06/30/2024 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5R21NS126092-02

Providence/Boston CFAR Supplemental Research Award: Contribution of persistently infected myeloid cells to neuroinflammation and neurotoxicity
06/01/2018 - 08/31/2019 (Subcontract PI)
The Miriam Hospital NIH NIAID
4P30AI042853-19



Title


Yr Title Project-Sub Proj Pubs

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

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  1. 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.View Related Profiles. PMID: 37961509; PMCID: PMC10634970; DOI: 10.1101/2023.11.01.565056;
     
  2. Jalloh S, Olejnik J, Berrigan J, Nisa A, Suder EL, Akiyama H, Lei M, Ramaswamy S, Tyagi S, Bushkin Y, Mühlberger E, Gummuluru S. CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses. PLoS Pathog. 2022 Oct; 18(10):e1010479.View Related Profiles. PMID: 36279285; PMCID: PMC9632919; DOI: 10.1371/journal.ppat.1010479;
     
  3. Jalloh S, Olejnik J, Berrigan J, Nisa A, Suder EL, Akiyama H, Lei M, Tyagi S, Bushkin Y, Mühlberger E, Gummuluru S. CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses. bioRxiv. 2022 Mar 30.View Related Profiles. PMID: 35378756; PMCID: PMC8978933; DOI: 10.1101/2022.03.29.486190;
     
  4. Akiyama H, Jalloh S, Park S, Lei M, Mostoslavsky G, Gummuluru S. Expression of HIV-1 Intron-Containing RNA in Microglia Induces Inflammatory Responses. J Virol. 2021 Mar 01; 95(5).View Related Profiles. PMID: 33298546; PMCID: PMC8092841; DOI: 10.1128/JVI.01386-20;
     
  5. Eshaghi B, Alsharif N, An X, Akiyama H, Brown KA, Gummuluru S, Reinhard BM. Stiffness of HIV-1 Mimicking Polymer Nanoparticles Modulates Ganglioside-Mediated Cellular Uptake and Trafficking. Adv Sci (Weinh). 2020 Sep; 7(18):2000649.View Related Profiles. PMID: 32999830; PMCID: PMC7509657; DOI: 10.1002/advs.202000649;
     
  6. Akiyama H, Gummuluru S. HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages. Viruses. 2020 06 30; 12(7).View Related Profiles. PMID: 32630058; PMCID: PMC7412260; DOI: 10.3390/v12070711;
     
  7. Wooten AK, Shenoy AT, Arafa EI, Akiyama H, Martin IMC, Jones MR, Quinton LJ, Gummuluru S, Bai G, Mizgerd JP. Unique Roles for Streptococcus pneumoniae Phosphodiesterase 2 in Cyclic di-AMP Catabolism and Macrophage Responses. Front Immunol. 2020; 11:554.View Related Profiles. PMID: 32300347; PMCID: PMC7145409; DOI: 10.3389/fimmu.2020.00554;
     
  8. Xu F, Bandara A, Akiyama H, Eshaghi B, Stelter D, Keyes T, Straub JE, Gummuluru S, Reinhard BM. Membrane-wrapped nanoparticles probe divergent roles of GM3 and phosphatidylserine in lipid-mediated viral entry pathways. Proc Natl Acad Sci U S A. 2018 09 25; 115(39):E9041-E9050.View Related Profiles. PMID: 30190430; PMCID: PMC6166840; DOI: 10.1073/pnas.1804292115;
     
  9. Akiyama H, Miller CM, Ettinger CR, Belkina AC, Snyder-Cappione JE, Gummuluru S. HIV-1 intron-containing RNA expression induces innate immune activation and T cell dysfunction. Nat Commun. 2018 08 27; 9(1):3450.View Related Profiles. PMID: 30150664; PMCID: PMC6110775; DOI: 10.1038/s41467-018-05899-7;
     
  10. Pena-Cruz V, Agosto LM, Akiyama H, Olson A, Moreau Y, Larrieux JR, Henderson A, Gummuluru S, Sagar M. HIV-1 replicates and persists in vaginal epithelial dendritic cells. J Clin Invest. 2018 08 01; 128(8):3439-3444.View Related Profiles. PMID: 29723162; PMCID: PMC6063466; DOI: 10.1172/JCI98943;
     
Showing 10 of 31 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 31 publications over 14 distinct years, with a maximum of 4 publications in 2014 and 2017 and 2020

YearPublications
20033
20071
20081
20092
20122
20131
20144
20152
20161
20174
20183
20204
20222
20231

Contact for Mentoring:

650 Albany St
Boston MA 02118
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