HIV infection is the leading killer worldwide among infectious diseases, incurring 2-3 million deaths annually. HIV has infected a total of more than 60 million people and over a third of them have died of AIDS. Defining the mechanisms of HIV transmission and understanding the role of immune cells and host factors that participate in the transmission process are essential in developing effective strategies to combat HIV infection. Our research focuses on the molecular mechanisms by which immune cells disseminate HIV. These studies can facilitate the development of more effective interventions against HIV infection and transmission.
Dendritic cells (DCs) perform an essential role in the induction and regulation of the adaptive immunity. Because DCs have a pivotal role in marshalling immune responses, HIV has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. DCs are among the first cell types to encounter and transmit HIV at the mucosa. To better understand the viral transmission mechanism, we are using molecular biological, cellular, and immunological approaches to define HIV interactions with DCs at the molecular level. Our studies have relevance to viral pathogenesis and the mucosal transmission of HIV. We are currently focusing on the molecular and cellular mechanisms underlying HIV-1 restriction by the host protein SAMHD1, which is the first identified mammalian dNTP triphosphohydrolase (dNTPase).
We also explore the novel role of SAMHD1 as a tumor suppressor in cutaneous T-cell lymphomas (CTCL). Achieving our goals will provide critical knowledge into a novel mechanism that regulates dNTP metabolism in malignant CD4+ T-cells, which will facilitate the development of more effective drugs against CTCL and other T-cell lymphomas. Discovery of the mechanisms leading to loss of SAMHD1 protein expression could support the development of strategies to re-induce SAMHD1 gene expression as a new therapeutic modality in CTCL or other types of cancer.
Current NIH-funded Projects in the Wu Lab
- Mechanisms of SAMHD1-mediated HIV-1 restriction in dendritic cells;
- HIV-1 Nef interaction with Nef-associated factor 1 in regulating viral latency;
- Mechanisms of HIV-1 RNA methylation in regulating viral replication;
- Novel role of SAMHD1 as a tumor suppressor in cutaneous T-cell lymphomas.