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.
- Kyoto University, PhD
- Kyoto University, BE/BEng
- Published on 9/6/2018
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. PMID: 30190430.
- Published on 8/27/2018
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. PMID: 30150664.
- Published on 7/9/2018
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. PMID: 29723162.
- Published on 10/13/2017
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). PMID: 28794041.
- Published on 10/4/2017
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. PMID: 28933537.
- Published on 9/20/2017
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. PMID: 28931903.
- Published on 6/9/2017
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). PMID: 28424288.
- Published on 8/11/2016
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. PMID: 27521724.
- Published on 4/14/2015
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. PMID: 25853367.
- Published on 3/11/2015
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. PMID: 25760631.
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