Hisashi Akiyama, Ph.D.
Research Assistant Professor of Microbiology
650 Albany Street, X343B
B.A. Kyoto University, Japan
Ph.D. Kyoto University, Japan
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.
- Kijewski SD, Akiyama H, Feizpour A, Miller CM, Ramirez NG, Reinhard BM, Gummuluru S. 2016. Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated. Virology 497:328-336. PMID: 27521724
- Yu X, Xu F, Ramirez NG, Kijewski SD, Akiyama H, Gummuluru S, Reinhard BM. 2015. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS Nano 9:4182-4192. PMID: 25853367
- Feizpour A, Yu X, Akiyama H, Miller CM, Edmans E, Gummuluru S, Reinhard BM. 2015. Quantifying lipid contents in enveloped virus particles with plasmonic nanoparticles. Small 11:1592-1602. PMID: 25382201
- Akiyama H, Ramirez NG, Gudheti MV, Gummuluru S. 2015. CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies. PLoS Pathog 11:e1004751. PMID: 25760631
- Yu X, Feizpour A, Ramirez NG, Wu L, Akiyama H, Xu F, Gummuluru S, Reinhard BM. 2014. Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells. Nat Commun 5:4136. PMID: 24947940
- Gummuluru S, Pina Ramirez NG, Akiyama H. 2014. CD169-dependent cell-associated HIV-1 transmission: a driver of virus dissemination. J Infect Dis 210 Suppl 3:S641-647. PMID: 25414418
- Akiyama H, Miller C, Patel HV, Hatch SC, Archer J, Ramirez NG, Gummuluru S. 2014. Virus particle release from glycosphingolipid-enriched microdomains is essential for dendritic cell-mediated capture and transfer of HIV-1 and henipavirus. J Virol 88:8813-8825. PMID: 24872578
- Schiralli Lester GM, Akiyama H, Evans E, Singh J, Gummuluru S, Henderson AJ. 2013. Interleukin 2-inducible T cell kinase (ITK) facilitates efficient egress of HIV-1 by coordinating Gag distribution and actin organization. Virology 436:235-243. PMID: 23260110
- *Puryear WB, *Akiyama H, Geer SD, Ramirez NP, Yu X, Reinhard BM, Gummuluru S. 2013. Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS Pathog 9:e1003291. PMID: 23593001
* Contributed equally.
- Sagar M, Akiyama H, Etemad B, Ramirez N, Freitas I, Gummuluru S. 2012. 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. J Infect Dis 205:1248-1257. PMID: 22396600
- Akiyama H, Ishimatsu M, Miura T, Hayami M, Ido E. 2008. 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. Microbes Infect 10:531-539. PMID: 18403228
- Akiyama H, Ido E, Akahata W, Kuwata T, Miura T, Hayami M. 2003. 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. J Gen Virol 84:1663-1669. PMID: 12810859
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