Molecular mechanisms of HIV immune evasion of the innate immune response in myeloid cells

Abstract

The expression of intrinsic antiviral factors by myeloid cells is a recently recognized mechanism of restricting lentiviral replication. Viruses that enter these cells must develop strategies to evade cellular antiviral factors to establish a productive infection. By studying the cellular targets of virally encoded proteins that are necessary to infect myeloid cells, a better understanding of cellular intrinsic antiviral strategies has now been achieved. Recent findings have provided insight into how the lentiviral accessory proteins, Vpx, Vpr and Vif counteract antiviral factors found in myeloid cells including SAMHD1, APOBEC3G, APOBEC3A, UNG2 and uracil. Here we review our current understanding of the molecular basis of how cellular antiviral factors function and the viral countermeasures that antagonize them to promote viral transmission and spread.

Figure 1

Genomic organization of HIV-1/SIVcpz, SIVagm and HIV-2/SIVsm [32]. HIV‑1 contains the vpu accessory gene, but not the vpx accessory gene. HIV-2 and SIVsm encode vpx but not vpu. SIVagm encodes neither vpu nor vpx.

Figure 2

Mechanisms in myeloid cells that inhibit HIV-1 reverse transcription. dNTPs are dephosphorylated by SAMHD1 (1). A high intracellular concentration of dUTP relative to dTTP in myeloid cells increases the incorporation of deoxyuridine into HIV-1 cDNA by reverse transcriptase (2). A3A deaminates cytidine to uridine in HIV-1 cDNA (3). A question mark (?) indicates that A3A may slow reverse transcription through an unknown mechanism. UNG2 catalyzes the removal of uracil from HIV-1 cDNA, and may lead to fragmentation or degradation of HIV-1 cDNA (4).