ASCT2 inhibits HIV-1 infectivity by promoting the incorporation of a gp160/ASCT2 complex into virions.

Restriction factors are type I interferon (IFN)-inducible proteins that provide an early line of defense against HIV-1. Our current findings propose the amino acid transporter ASCT2 as a new host plasma membrane transporter that restricts the infectivity of HIV-1 viral particles. Our results show that ASCT2 is constitutively expressed in CD4 IMPORTANCE: Globally, there are about 39 million people living with HIV (PLWH). Antiretroviral treatment (ART) has transformed HIV infection into a chronic condition. However, effective ART does not cure HIV since the virus establishes long-lasting reservoirs that are resistant to currently available ART. Nowadays, the choice of the ART regimen depends on several factors, such as drug resistance, health conditions of PLWH, and possible side effects of medications. To address the complexity of the ART regimen, drug toxicities, and drug resistance, the research on novel formulations continues. Currently, new antiviral therapies are being developed that target important interactions between viral accessory proteins and host restriction factors, such as the interaction between Vpu and BST-2 and between Vif and APOBEC3. Therefore, our current findings about ASCT2 and Vpu not only provide novel insights about HIV-1 virus-host restriction factor interaction but also propose a novel and promising strategy to develop a new treatment against HIV.