HIV-1 Exploits CLASP2 To Induce Microtubule Stabilization and Facilitate Virus Trafficking to the Nucleus
Sahana Mitra, Shanmugapriya Shanmugapriya, Eveline Santos da Silva, Mojgan H. Naghavi
Abstract
While microtubules (MTs) have long been known to be important for delivery of incoming HIV-1 cores to the nucleus, how the virus engages and exploits these filaments remains poorly understood. Our previous work revealed the importance of highly specialized MT regulators that belong to a family called plus-end tracking proteins (+TIPs) in facilitating early stages of infection. These +TIPs perform various functions, such as engaging cargos for transport or engaging peripheral actin to stabilize MTs, suggesting several family members have the potential to contribute to infection in different ways. Here, we reveal that cytoplasmic linker-associated protein 2 (CLASP2), a key regulator of cortical capture and stabilization of MTs, interacts with incoming HIV-1 particles, and we identify a distinct C-terminal domain in CLASP2 that promotes both MT stabilization and early infection. Our findings identify a new +TIP acting as a host cofactor that facilitates early stages of viral infection.