Hisashi Akiyama
Research Assistant Professor
Boston University School of Medicine
Dept of Microbiology

PhD, 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.


PROVIDENCE/BOSTON CFAR SUPPLEMENTAL RESEARCH AWARD: CONTRIBUTION OF PERSISTENTLY INFECTED MYELOID CELLS TO NEUROINFLAMMATION AND NEUROTOXICITY
06/01/2018 - 05/31/2019 (PI)
The Miriam Hospital NIH NIAID
4P30AI042853-19




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.

  1. 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.
     
  2. 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 Aug 27; 9(1):3450.View Related Profiles. PMID: 30150664.
     
  3. 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 Aug 01; 128(8):3439-3444.View Related Profiles. PMID: 29723162.
     
  4. Akiyama H, Ramirez NP, Gibson G, Kline C, Watkins S, Ambrose Z, Gummuluru S. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon. J Virol. 2017 Nov 01; 91(21).View Related Profiles. PMID: 28794041.
     
  5. Feizpour A, Stelter D, Wong C, Akiyama H, Gummuluru S, Keyes T, Reinhard BM. Membrane Fluidity Sensing on the Single Virus Particle Level with Plasmonic Nanoparticle Transducers. ACS Sens. 2017 Oct 27; 2(10):1415-1423.View Related Profiles. PMID: 28933537.
     
  6. Nazari M, Xi M, Lerch S, Alizadeh MH, Ettinger C, Akiyama H, Gillespie C, Gummuluru S, Erramilli S, Reinhard BM. Plasmonic Enhancement of Selective Photonic Virus Inactivation. Sci Rep. 2017 Sep 20; 7(1):11951.View Related Profiles. PMID: 28931903.
     
  7. Miller CM, Akiyama H, Agosto LM, Emery A, Ettinger CR, Swanstrom RI, Henderson AJ, Gummuluru S. Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells. J Virol. 2017 Jul 01; 91(13).View Related Profiles. PMID: 28424288; DOI: 10.1128/JVI.00051-17;.
     
  8. Kijewski SD, Akiyama H, Feizpour A, Miller CM, Ramirez NG, Reinhard BM, Gummuluru S. Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated. Virology. 2016 Oct; 497:328-36.View Related Profiles. PMID: 27521724; PMCID: PMC5026622; DOI: 10.1016/j.virol.2016.07.029;.
     
  9. Yu X, Xu F, Ramirez NG, Kijewski SD, Akiyama H, Gummuluru S, Reinhard BM. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS Nano. 2015; 9(4):4182-92.View Related Profiles. PMID: 25853367; PMCID: PMC4423798; DOI: 10.1021/acsnano.5b00415;.
     
  10. Akiyama H, Ramirez NG, Gudheti MV, Gummuluru S. CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies. PLoS Pathog. 2015 Mar; 11(3):e1004751.View Related Profiles. PMID: 25760631; PMCID: PMC4356592; DOI: 10.1371/journal.ppat.1004751;.
     
Showing 10 of 24 results. Show More

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

Bar chart showing 24 publications over 11 distinct years, with a maximum of 4 publications in 2014 and 2017

YearPublications
20033
20071
20081
20092
20122
20131
20144
20152
20161
20174
20183
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72 E. Concord St Housman (R)
Boston MA 02118
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