The Roles of Coinhibitory Receptors in Pathogenesis of Human Retroviral Infections

Costimulatory and coinhibitory receptors play a key role in regulating immune responses to infection and cancer. Coinhibitory receptors include programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin and ITIM domain (TIGIT), which suppress immune responses. Coinhibitory receptors are highly expressed on exhausted virus-specific T cells, indicating that viruses evade host immune responses through enhanced expression of these molecules. Human retroviruses, human immunodeficiency virus (HIV) and human T-cell leukemia virus type 1 (HTLV-1), infect T cells, macrophages and dendritic cells. Therefore, one needs to consider the effects of coinhibitory receptors on both uninfected effector T cells and infected target cells. Coinhibitory receptors are implicated not only in the suppression of immune responses to viruses by inhibition of effector T cells, but also in the persistence of infected cells in vivo. Here we review recent studies on coinhibitory receptors and their roles in retroviral infections such as HIV and HTLV-1.