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. 2014 May;35(3):186-95.
doi: 10.11813/j.issn.0254-5853.2014.3.186.

Replication potentials of HIV-1/HSIV in PBMCs from northern pig-tailed macaque (Macaca leonina)

Ai-Hua Lei  1 , Gao-Hong Zhang  2 , Ren-Rong Tian  1 , Jia-Wu Zhu  1 , Hong-Yi Zheng  3 , Wei Pang  4 , Yong-Tang Zheng  5
Affiliations

Replication potentials of HIV-1/HSIV in PBMCs from northern pig-tailed macaque (Macaca leonina)

Ai-Hua Lei et al. Dongwuxue Yanjiu. 2014 May.

Abstract

The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1NL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.

Keywords: HIV-1; HSIV; Northern pig-tailed macaque (Macaca leonina); PBMC; Replication.

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Figures

Figure 1
Figure 1
Schematic representation of viral clones used in this study
Infections of four different macaque donors are shown; Experiments were carried out with equal amounts of viruses (40 pg p24); Replication was monitored by determining the amount of p24 in culture supernatants every three days post-infection. NPM: northern pig-tailed macaque (<italic>M. leonina</italic>)
Figure 2
Replication of HIV-1 strains in M. leonina PBMCs
mRNA expression levels of human and macaque cells normalized to GAPDH and RPL13A mRNA using the 2<sup>-ΔCt</sup>× 100% method, respectively; Mean values of PBMCs isolations from three healthy donors are shown, and error bars represent standard errors of the means. hPBMC: human PBMCs; NPM: <italic>M.leonina</italic>; ChRM: Chinese rhesus macaque.
Figure 3
TRIM5 and APOBEC3G/3F mRNA expression in human and macaque cells
A, B and C are replication of HIV and HSIV in H9 and human PBMCs (hPBMCs), <italic>M. leonina</italic> (NPM) PBMCs, and Chinese rhesus macaque (ChRM) PBMCs, respectively; Infections were carried out at an MOI of 0.01; Replication was monitored by determining the amount of p24 (for HIV/HSIV) or p27 (for SIV<sub>mac239</sub>) per mL at 3- to 4-day intervals post-infection; Cells and donors are indicated at the top of each panel. <italic>M.leonina</italic>; ChRM: Chinese rhesus macaque.
Figure 4
Replication of HIV and HSIV chimeras in vitro
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