Our research is broadly focused on the role of dendritic cells (DCs) in the initiation and propagation of HIV-1 replication. Since dendritic cells are believed to be the first immune competent cells to encounter virus in the genital mucosa, a thorough understanding of the HIV-DC interactions is of paramount importance. DCs can capture virus particles independently of CD4 and co-receptor complexes, and retain them in an infectious state for an extended period of time. These virus-bearing DCs may then facilitate a more efficient spread of virus to replication-permissive CD4+ T cells. Our recent work has identified a novel glycosphingolipid dependent mechanism of virus attachment to DCs. The fate of the virus particle post-attachment in DCs remains unclear. Virion trafficking within the DC bypasses conventional endocytic organelles, i.e., endosomes and lysosomes. Virus localization within this novel vesicular compartment not only has the potential to protect the invading HIV from being degraded, but also creates a latent reservoir of virus, which could present a major challenge for eradication by antiretroviral therapy. Furthermore, the mechanism of subsequent return of infectious virus particles to the cell surface and the method of subsequent transmission to T cells remains unclear. Current studies utilizing biochemical and microscopic approaches are underway to monitor HIV-1 trafficking and localization in the DC and its subsequent transfer to T cells.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- University of Rochester, PhD
- University of Rochester, MS
- University of Saskatchewan, BSc
- 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 08 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 7/12/2017
Ruedas JB, Ladner JT, Ettinger CR, Gummuluru S, Palacios G, Connor JH. Spontaneous Mutation at Amino Acid 544 of the Ebola Virus Glycoprotein Potentiates Virus Entry and Selection in Tissue Culture. J Virol. 2017 Aug 01; 91(15). PMID: 28539437.
- Published on 6/30/2017
Kozlowski E, Wasserman GA, Morgan M, O'Carroll D, Ramirez NP, Gummuluru S, Rah JY, Gower AC, Ieong M, Quinton LJ, Mizgerd JP, Jones MR. The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses. PLoS One. 2017; 12(6):e0179797. PMID: 28665939.
- 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 11/22/2016
Ahi YS, Zhang S, Thappeta Y, Denman A, Feizpour A, Gummuluru S, Reinhard B, Muriaux D, Fivash MJ, Rein A. Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins. MBio. 2016 Nov 22; 7(6). PMID: 27879338.
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