Antiretroviral restriction factors

Abstract

Studies of retroviruses have been instrumental in revealing the existence of an array of antiviral proteins, or restriction factors, and the mechanisms by which they function. Some restriction factors appear to specifically inhibit retrovirus replication, while others have a broader antiviral action. Here, we briefly review current understanding of the mechanisms by which several such proteins exert antiviral activity. We also discuss how retroviruses have evolved to evade or antagonize antiviral proteins, including through the action of viral accessory proteins. Restriction factors, their viral targets and antagonists have exerted evolutionary pressure on each other, resulting in specialization and barriers to cross-species transmission. Potentially, this recently revealed intrinsic system of antiviral immunity might be mobilized for therapeutic benefit.

Figure. Factors and events in the restriction of retroviral replication by host proteins

Key retroviral restriction factors are shown in red, antagonists expressed by the HIV/SIV retroviruses are shown in green. Cellular cofactors, co-opted by viral antagonists are shown in purple. Key events or processes in the restriction of retroviral replication or associated with the action of the antagonists are indicated. The process of APOBEC3-mediated hypermutation is depicted in detail in the inset panel.