Fig. 1: Cytoplasmic host cell restrictions to human immunodeficiency virus types 1 (HIV‑1) infection and virally encoded antagonists. Schematic depiction of the HIV‑1 life cycle in the cytoplasm of a target cell with some restriction factors (RF) and their viral antagonists indicated. Early post entry steps of HIV‑1 replication are particularly targeted by host cell restriction factors including TRIM5α and Mx2 that recognize viral cores and may affect their stability. Uncoating of viral capsids renders viral RNA genomes accessible to host cell nucleases such as TREX1 that reduce innate immune recognition by the host cell and thus benefit HIV replication. Such a strategy may be exploited by the HIV‑1 Vpr protein that activates the SLX4 endonuclease complex. Reverse transcription of viral RNA genomes into DNA is targeted by the cytidine deaminase activity of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins and the triphosphohydrolase SAMHD1, which are antagonized by the viral proteins Vif and Vpx (Vpx is only encoded bythe human immunodeficiency virus type 2 (HIV‑2) and the simian immunodeficiency virus (SIV) and is lacking in HIV‑1). Reverse transcription products are recognized by cytoplasmic DNA sensors such as cGAS and Ifi-16 to trigger innate immune responses. During virus production, translation of viral mRNA can be restricted by Schlafen11 (SLFN11). At the late stages of particle production, viral progeny is trapped at the cell surface by tetherin (THN), a restriction antagonized by Vpu. The infectivity of released particles can be significantly compromised by the newly described restriction factors serine incorporator 3 and 5 (SERINC3/5) and their antiviral activity is antagonized by Nef.
From: Fackler, O.T. (2015). Spotlight on HIV‑1 Nef: SERINC3 and SERINC5 identified as restriction factors antagonized by the pathogenesis factor. Viruses, 7: 6730 — 6738.