{"id":15,"date":"2016-06-03T04:14:45","date_gmt":"2016-06-03T04:14:45","guid":{"rendered":"http:\/\/labs.icahn.mssm.edu\/bchenlab\/?page_id=15"},"modified":"2026-08-05T15:03:44","modified_gmt":"2026-08-05T15:03:44","slug":"research-projects","status":"publish","type":"page","link":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/research-projects\/","title":{"rendered":"Projects"},"content":{"rendered":"
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Mechanisms of HIV cell-to-cell transmission<\/strong><\/p>\n

CD4 helper T cells are by nature highly interactive cells, interrogating other immune cells for signs of infection or disrupted homeostasis. It therefore seems highly opportunistic that the human immunodeficiency virus type 1 (HIV-1), which infects CD4 T cells, can spread through contacts between HIV-infected and uninfected T cells that lead to infection-enhancing structures called virological synapses (VS). VS are initiated by the HIV surface Env glycoprotein on the infected cell and CD4 on the target cell. We have designed and employed infectious fluorescent HIV-1 to visualize and quantify viral transfer across the VS. High resolution, live video rate confocal microscopy allowed us to directly record the changes in viral protein distribution that occur during VS formation. We have characterized the efficient transfer of viral particles into target T cells through an endocytic route. Our ongoing studies are directed at understanding how cell-to-cell affects the number of viral copies per cell are generated, and testing how this may promote the high genetic diversity of HIV, and promote immune evasion.<\/p>\n<\/div>\n

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Evasion of antibody responses by virological synapses<\/strong><\/p>\n

The VS-mediated viral infection can be resistant to patient antibodies that are capable of neutralizing homologous cell free virus. We are working to understand how the VS provides a mechanism for HIV to evade humoral immune responses. \u00a0We found that the cytoplasmic tail of the Env glycoprotein, which is plays an important role in regulating fusion activity of Env, plays a role in the resistance of cell-cell infection to neutralization. Studies have revealed that endocytic trafficking and cellular sorting of the Env glycoprotein allows it assume distinct states on the surface of cells as compared to viruses. This can explain to a significant degree how cell-cell transmission resists neutralization by native antibody responses. To effectively target HIV infection and dissemination, we are studying patient neutralizing responses and considering optimal immunological approaches that can clear the HIV-1 reservoir.<\/p>\n<\/div>\n

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Modeling HIV-1 reservoirs in humanized mice<\/strong>\u00a0<\/b><\/span><\/p>\n

Although antiretroviral treatment is very effective at limiting the spread of HIV, the persistence of virus in latent pools within memory T cell thwarts the ability of the immune system to eliminate the virus from the body. As a result, when antiretroviral treatment is stopped, virus replication immediately resumes at a high rate. A current challenge in the field is therefore to find a way to identify the cells that harbor latent virus, and to find ways to eliminate them either by activating the virus within them or by somehow targeting them for destruction. To address the problem of latency, we are building genetic reporter mouse models that can become irreversibly marked when HIV infects the cells. The cells that persist and harbor latent virus remain marked even in the presence of antiretroviral therapy. The marking system is designed to help uncover specific genes or cell states that distinguish latent HIV reservoirs from non-infected cells. We are Developments in iPS derived stem cell models to create new genetic models to definitively understand the genetics and epigenetics of HIV latency and persistence.<\/p>\n

Tools to Support HIV Cure<\/strong><\/p>\n

We are developing cell-based assays that utilize our deep understanding of HIV transmission dynamics to efficiently evaluate the sensitivity of diverse viral populations within individuals to antibody-based treatments. These rapid assays for assessing the neutralization sensitivity of viruses in an individual\u2019s HIV reservoir are critical for identifying patients most likely to benefit from antibody therapies. Our research has also uncovered novel strategies to reactivate latent HIV with minimal effects on uninfected bystander cells. Gene-targeted approaches currently in use include the delivery of HIV Tat mRNA alongside CRISPR activation (CRISPRa) to selectively induce viral reactivation within patient-derived T cells. This targeted reactivation is a key step toward purging the latent viral reservoir and advancing toward a functional cure.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Mechanisms of HIV cell-to-cell transmission CD4 helper T cells are by nature highly interactive cells, interrogating other immune cells for signs of infection or disrupted homeostasis. It therefore seems highly opportunistic that the human immunodeficiency virus type 1 (HIV-1), which infects CD4 T cells, can spread through contacts between HIV-infected and uninfected T cells that […]<\/p>\n","protected":false},"author":77,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-15","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/pages\/15","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/users\/77"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/comments?post=15"}],"version-history":[{"count":11,"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/pages\/15\/revisions"}],"predecessor-version":[{"id":165,"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/pages\/15\/revisions\/165"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/bchenlab\/wp-json\/wp\/v2\/media?parent=15"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}