The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells
Fig 5
SIVs deficient in degrading SAMHD1 in memory CD4+ T cells exhibit an attenuated replication phenotype in inoculated rhesus macaques.
Rhesus macaques were inoculated intrarectally with 1 x 104 TCID50 of SIVmac239 WT or SIVmac239 X-Q76A derivatives (A and C) or 1 x 103 TCID50 of SIVmac316 WT or the SIVmac316X-Q76A derivatives (B and D). The infectious virus titers in the inocula were determined by end-point dilution using SAMHD1 negative SupT1-R5 cells to avoid suppressive effects of SAMHD1 restriction. Plasma viral copies/ml are shown in panel A and C. Memory CD4+ T cell counts/μl are shown in panel C and D. Black curves: WT virus; blue curves: putative revertant Vpx mutants; red curves: non-revertant Vpx mutants. (E) Amino acid substitutions present in the starting Q76A Vpx mutant virus or in the putative revertant virus populations present in the plasmas of macaques K42 and JAX4 at week 35 PI, based on SGA (see Fig 6) are shown. The locations of the three helical domains of SIVmac Vpx are indicated.