Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the T_FH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary

Human immunodeficiency virus (HIV) infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV. Identifying and eliminating the HIV reservoir will prevent viral rebound and cure HIV infection. In this review, we focus on a recently discovered HIV reservoir in a subset of CD4⁺ T cells called the follicular helper T (T_FH) cells. We describe the potential mechanisms for the emergence of reservoir in T_FH cells, and the strategies to target and eliminate this viral reservoir.