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.
The northern pig-tailed macaque(NPM,Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northern pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age(P>0.05), while serum IgG levels increased progressively with age(r=0.202;P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males(P<0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4(r=0.700; P<0.0001). This study provides basic serum immunoglobulin and complement data of captive northern pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
TRIM5α restricts retroviruses in a species-specific manner. Cyclophilin A was independently retrotransposed into the TRIM5 loci in different species, leading to the generation of antiviral TRIM5-cyclophilin A(TRIMCyp) proteins. Previously, we found that assam macaques express a TRIMCyp chimera(am TRIMCyp), along with a TRIM5α allelic protein(am TRIM5α). Herein,we investigated the antiviral activity of am TRIMCyp and am TRIM5α individually, as well as their interaction and joint effects.am TRIMCyp showed a divergent restriction pattern from am TRIM5α. Although both proteins potently restricted the replication of HIV-1, only am TRIM5α inhibited N-MLV. Remarkably, cellular anti-HIV-1 activity increased when am TRIMCyp and am TRIM5α were coexpressed, indicating a synergistic block of HIV-1 replication. Consistently, PMBCs from heterozygous am TRIM5α/TRIMCyp showed stronger resistance to HIV-1 infection than those from am TRIM5α/TRIM5α homozygotes. The anti-HIV-1 synergistic effect was dependent on the am TRIMCyp-am TRIM5α interaction. In contrast, am TRIMCyp completely abrogated the anti-N-MLVactivity mediated by am TRIM5α, showing a dominant-negative effect, indicating that the generation of am TRIMCyp was involved in the trade-off between divergent restriction activities. Our results provide a new paradigm to study functional trade-offs mediated by allelic proteins, a theoretical basis for utilizing animal models with various TRIM5 alleles, as well as novel HIV-1 gene therapy strategies.
Dan MuJia-Wu ZhuFeng-Liang LiuHong-Yi ZhengYong-Tang Zheng
Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.
Non-human primates such as Chinese rhesus macaques are the favorable models for preclinical study of potential therapeutic drugs,vaccines and mechanisms of human diseases.Little is known about the normal levels of leukocyte subpopulations of Chinese rhesus macaques.To obtain these data,100 blood samples from Chinese rhesus macaques were collected.The normal range of major leukocyte subpopulations,such as T lymphocytes,B lymphocytes,monocytes,myeloid dendritic cells(mDCs)and plasmacytoid dendritic cells(pDCs),were quantitatively analyzed by flow cytometry through BD trucount tubes.The influence of age and sex on the cell counts of leukocyte subpopulations was analyzed.The counts of CD3^(+)T cells,CD3+CD4^(+)T cells,CD3+CD8^(+)T cells and B cells decreased with age,but those of monocytes,mDCs and pDCs had no significant correlation with age.Significant differences existed in the cell counts of most leukocyte subpopulations between the male and female groups except pDCs.Furthermore the values of the females were higher than those of the males.The study provided basic information about the leukocyte subpopulations of Chinese rhesus macaques,and it may be valuable for immunobiological study of Chinese rhesus macaques.
