Tim Hanley Research Lab

Latent HIV-1 infection in macrophages

The major barrier toward the eradication of human immunodeficiency virus type 1 (HIV-1) infection is the presence of a small reservoir of latently or persistently infected cells, including CD4+ T cells and macrophages. The Hanley lab is actively involved in understanding the cellular and viral constituents that contribute to the establishment and maintenance of the latent HIV-1 reservoir in myeloid cells such as macrophages. We aim to provide new insights into the ability of HIV-1 to establish persistent infection in myeloid cells and to identify novel targets for therapeutic intervention.

HIV-1 detection by macrophages

HIV-1 infection of macrophages leads to the generation of an innate immune response characterized by the production of type I interferons (IFNs) and the expression of numerous IFN-regulated genes (IRGs). Multiple studies have demonstrated that HIV-1 can be sensed by a diverse set of innate immune receptors, including Toll-like receptors (TLRs) and nucleic acid sensors such as RIG-I and cGAS, leading to the production of type I IFNs. One focus of our lab is determining how HIV-1 is sensed in macrophages and the downstream effects of viral sensing on HIV-1 replication in macrophages.

Sex-based differences in HIV-1 infection

Biological sex is a critical factor influencing the course of HIV-1 disease and progression to acquired immune deficiency syndrome (AIDS). We and others have shown that macrophages derived from female donors are more resistant to infection with HIV-1 than macrophages derived from male donors. This relative resistance is due, at least in part, to the differential regulation of an intrinsic antiviral protein called sterile alpha motif and HD-domain-containing protein 1 (SAMHD1). Our current studies seek to understand the cellular determinants of SAMHD1 regulation in macrophages from female donors, with a focus on IFNs and IRGs.