Rahm Gummuluru

Gummuluru and his lab are using genetic, immunological and biochemical approaches to identify the molecular mechanisms of human immunodeficiency virus (HIV) – dendritic cell (DC) interactions, and the putative contributions of viral accessory genes to HIV-1 replication in DC- T cell co-cultures.

The research in my laboratory is broadly focused on the role of dendritic cells (DC) in the initiation and propagation of HIV-1 replication, and the mechanism of subversion of DC program by the virus. Since dendritic cells are believed to be the first immune competent cells to encounter virus in the genital mucosa, a thorough understanding of HIV-DC interactions is of paramount importance. DC 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 DC may then facilitate a more efficient spread of virus to replication-permissive CD4+ T cells. DC-SIGN, a mannose binding C-type lectin receptor, is one virus-attachment factor that captures infectious virus particles, and facilitates trans-infection of CD4+ T cells. Our previous work has identified DC-SIGN independent mechanisms of virus attachment by DC. Hence, we are utilizing novel genetic screens to identify virus-capture mechanisms displayed by dendritic cells. The fate of the virus particle post-attachment, be it via DC-SIGN, or other molecules, in DC also remains unclear. Virion trafficking within DC also seems to bypass 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 that 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 virus transmission to T cells remains unclear.

Current studies utilizing biochemical and microscopic approaches to delineate molecular pathways are underway to monitor HIV-1 trafficking and localization in the DC and its subsequent transfer to T cells. These studies will aid in our understanding of the mechanism of HIV transmission to the naïve host and might lead to the identification of novel therapies that prevent establishment of virus infection.

Selected Publications

1. Kijewski, S.D. and Gummuluru, S. 2015. A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection; the Story so far. Future Virol. 10:257-269. PMID 26213560
2. Yu, X., Xu, F., Ramirez, N.G., Kijewski, S.D., Akiyama, H, Gummuluru, S.*, and Reinhard, B.M.* 2015. Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological Synapse. ACS Nano. 9:4182-4192. PMID 25853367 (*co-corresponding authors).
3. Akiyama, H., Ramirez, N.G., Gudheti, M.V., and Gummuluru, S. 2015. CD-169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in Dendritic Cells Attenuates Efficacy fo Anti-gp120 Broadly Neutralizing Antibodies. PLoS Pathog. 11:e1004751. PMID 25760631